Rubella virus vaccine, live

MERUVAX® II (Rubella Virus Vaccine Live) is a live virus vaccine for vaccination against rubella (German measles).

MERUVAX (rubella virus vaccine live) 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 WI-38 human diploid lung fibroblasts.1,2

The growth medium is Minimum Essential Medium (MEM) [a buffered salt solution containing vitamins and amino acids and supplemented with fetal bovine serum] containing human serum albumin and neomycin. Sorbitol and hydrolyzed gelatin stabilizer are added to the individual virus harvests.

The cells, virus pools, fetal bovine serum, and human albumin are all screened for the absence of adventitious agents. Human albumin is processed using the Cohn cold ethanol fractionation procedure.

The reconstituted vaccine is for subcutaneous administration. Each 0.5 mL dose contains not less than 1,000 TCID50 (tissue culture infectious doses) of rubella virus. Each dose of the vaccine is calculated to contain sorbitol (14.5 mg), sodium phosphate, sucrose (1.9 mg), sodium chloride, hydrolyzed gelatin (14.5 mg), human albumin (0.3 mg), fetal bovine serum ( < 1 ppm), other buffer and media ingredients and approximately 25 mcg of neomycin. The product contains no preservative.

Before reconstitution, the lyophilized vaccine is a light yellow compact crystalline plug. MERUVAX (rubella virus vaccine live) II, when reconstituted as directed, is clear yellow.

REFERENCES

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.

No. 4673/4309 MERUVAX (rubella virus vaccine live) II is supplied as follows: (1) a box of 10 single-dose vials of lyophilized vaccine (package A) NDC 0006-4673-00; and (2) a box of 10 vials of diluent (package B). To conserve refrigerator space, the diluent may be stored separately at room temperature.

Storage

During shipment, to ensure that there is no loss of potency, the vaccine must be maintained at a temperature of 10°C (50°F) or colder. Freezing during shipment will not affect potency.

Protect the vaccine from light at all times, since such exposure may inactivate the virus.

Before reconstitution, store the vial of lyophilized vaccine at 2-8°C (36-46°F) or colder. The diluent may be stored in the refrigerator with the lyophilized vaccine or separately at room temperature.

It is recommended that the vaccine be used as soon as possible after reconstitution. 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.

REFERENCE

21. Centers for Disease Control and Prevention. Recommended childhood immunization schedule — United States, January-June 1996, MMWR 44(51 & 52): 940-943, January 5, 1996.

22. Rubella Prevention: Recommendation of the Immunization Practices Advisory Committee (ACIP), MMWR 39(RR-15): 1-18, November 23, 1990.

23. Measles Prevention: Recommendations of the Immunization Practices Advisory Committee (ACIP), MMWR 38(S-9): 5-22, December 29, 1989.

24. Jong, E.G.: The Travel and Tropical Medicine Manual, W.B. Saunders Company, p. 12-16, 1987.

25. Committee on Immunization Council of Medical Societies, American College of Physicians, Phila., PA, Guide for Adult Immunization, First Edition, 1985.

26. General Recommendations on Immunization, Recommendations of the Advisory Committee on Immunization Practices, MMWR 43(RR-1): 1-38, January 28, 1994.

39. Measles, Mumps, and Rubella — Vaccine Use and Strategies for Elimination of Measles, Rubella, and Congenital Rubella Syndrome and Control of Mumps: Recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR 47(RR-8): May 22, 1998.

Manuf. and Dist. by: Merck and Co., INC, Whitehouse station, NJ 08889, USA. FDA Rev date: Jan 2007

Hypersensitivity to any component of the vaccine, including gelatin.

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 INDICATIONS AND USAGE , Non-Pregnant Adolescents and Adult Females and PRECAUTIONS , Pregnancy ).

Anaphylactic or anaphylactoid reactions to neomycin (each dose of reconstituted vaccine contains approximately 25 mcg of neomycin).

Febrile respiratory illness or other active febrile infection. However, the ACIP has recommended that all vaccines can be administered to persons with minor illnesses such as diarrhea, mild upper respiratory infection with or without low-grade fever, or other low-grade febrile illness.

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.

General

Adequate treatment provisions including epinephrine injection (1:1000), should be available for immediate use should an anaphylactic or anaphylactoid reaction occur.

Special care should be taken to ensure that the injection does not enter a blood vessel.

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 ).

Children and young adults who are known to be infected with human immunodeficiency viruses and are not immunosuppressed may be vaccinated. However, vaccinees who are infected with HIV should be monitored closely for vaccine-preventable diseases because immunization may be less effective than for uninfected persons (see CONTRAINDICATIONS ).

Vaccination should be deferred for 3 months or longer following blood or plasma transfusions, or administration of immune globulin (human). 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.

Individuals with active untreated tuberculosis should not be vaccinated.

As for any vaccine, vaccination with MERUVAX II may not result in protection in 100% of vaccinees.

The health-care provider should determine the current health status and previous vaccination history of the vaccinee.

The health-care provider should question the patient, parent, or guardian about reactions to a previous dose of MERUVAX II or other measles-, mumps-, or rubella-containing vaccines.

Information For Patients

The health-care provider should provide the vaccine information required to be given with each vaccination to the patient, parent or guardian.

The health-care provider should inform the patient, parent or guardian of the benefits and risks associated with vaccination. For risks associated with vaccination see WARNINGS , PRECAUTIONS , ADVERSE REACTIONS .

Patients, parents or guardians should be instructed to report any serious adverse reactions to their health-care provider who in turn should report such events to the U.S. Department of Health and Human Services through the Vaccine Adverse Event Reporting System (VAERS), 1-800-822-7967.

Pregnancy should be avoided for three months following vaccination, and patients should be informed of the reasons for this precaution (see INDICATIONS AND USAGE , Non-Pregnant Adolescent and Adult Females , CONTRAINDICATIONS , and PRECAUTIONS , Pregnancy ).

Laboratory Tests

See INDICATIONS AND USAGE , Non-Pregnant Adolescents and Adult Females , for Rubella Susceptibility Testing, and CLINICAL PHARMACOLOGY .

Immunosuppressive Therapy

The immune status of patients about to undergo immunosuppressive therapy should be evaluated so that the physician can consider whether vaccination prior to the initiation of treatment is indicated. (see CONTRAINDICATIONS and PRECAUTIONS ).

The ACIP has stated that "patients with leukemia in remission who have not received chemotherapy for at least 3 months may receive live-virus vaccines. Short-term (<2 weeks), low- to moderate-dose systemic corticosteroid therapy, topical steroid therapy (e.g., nasal, skin), long-term alternate-day treatment with low to moderate doses of short-acting systemic steroid, and intra-articular, bursal, or tendon injection of corticosteroids are not immunosuppressive in their usual doses and do not contraindicate the administration of rubella vaccine."

Immune Globulin

Administration of immune globulins concurrently with MERUVAX II may interfere with the expected immune response.

See also PRECAUTIONS , General .

Carcinogenesis, Mutagenesis, Impairment of Fertility

MERUVAX II has not been evaluated for carcinogenic or mutagenic potential, or potential to impair fertility.

Pregnancy

Pregnancy Category C

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. Therefore, rubella vaccine should not be administered to pregnant females (see INDICATIONS AND USAGE , Non-Pregnant Adolescent and Adult Females and 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 MERUVAX II is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in infants below the age of 12 months have not been established (see INDICATIONS AND USAGE , Recommended Vaccination Schedule ).

Geriatric Use

Clinical studies of MERUVAX II did not include sufficient numbers of seronegative subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects.