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CLINICAL PHARMACOLOGY Clinical studies of 73 double seronegative children 12 months to 2 years of age demonstrated that BIAVAX (rubella and mumps virus vaccine live) II is highly immunogenic and generally well tolerated. In these studies, a single injection of the vaccine induced rubella hemagglutination-inhibition (HI) antibodies in 100 percent, and mumps neutralizing antibodies in 97 percent of the susceptible children. The RA 27/3 rubella strain in BIAVAX (rubella and mumps virus vaccine live) II 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 following administration of BIAVAX (rubella and mumps virus vaccine live) II have been shown to persist for at least two years without substantial decline. Antibody levels after immunization with BIAVAX (Rubella and Mumps Virus Vaccine Live), containing the HPV-77 strain of rubella, have persisted for 10.5 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.

DESCRIPTION BIAVAX (rubella and mumps virus vaccine live) ® II (Rubella and Mumps Virus Vaccine Live) is a live virus vaccine for immunization against rubella (German measles) and mumps. BIAVAX (rubella and mumps virus vaccine live) II is a sterile lyophilized preparation of the Wistar RA 27/3 strain of live attenuated rubella virus grown in human diploid cell (WI-38) culture; and the Jeryl Lynn (B level) strain of mumps virus grown in cell cultures of chick embryo. The vaccine viruses are the same as those used in the manufacture of MERUVAX* II (Rubella Virus Vaccine Live) and MUMPSVAX* (Mumps Virus Vaccine Live). The two viruses are mixed before being lyophilized. 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 TCID 50 of the U.S. Reference Rubella Virus and 20,000 TCID 50 of the U.S. Reference Mumps Virus. Each dose contains approximately 25 mcg of neomycin. The product contains no preservative. Sorbitol and hydrolized gelatin are added as stabilizers.

INDICATIONS BIAVAX (rubella and mumps virus vaccine live) II is indicated for simultaneous immunization against rubella and mumps in persons 12 months of age or older. A booster is not needed. The vaccine is not recommended for infants younger than 12 months because they may retain maternal rubella and mumps neutralizing antibodies which may interfere with the immune response. 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. 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. 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 reasons 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 ). Postpartum Women It has been found convenient in many instances to vaccinate rubella-susceptible women in the immediate postpartum period. (See Nursing Mothers ). 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 BIAVAX (rubella and mumps virus vaccine live) II. BIAVAX (rubella and mumps virus vaccine live) II should not be given less than one month before or after administration of other virus vaccines. *Registered trademark of MERCK & CO., INC. **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." DOSAGE AND ADMINISTRATIONFOR SUBCUTANEOUS ADMINISTRATION Do not inject intravenously. The dosage of vaccine is the same for all persons. Inject the total volume (about 0.5 mL) of reconstituted vaccine subcutaneously, preferably into the outer aspect of upper arm. Do not give immune globulin (IG) concurrently with BIAVAX (rubella and mumps virus vaccine live) II. During shipment, to insure that there is no loss of potency, the vaccine must be maintained at a temperature of 10°C (50°F) or less. Before reconstitution, store BIAVAX (rubella and mumps virus vaccine live) 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 of the vaccine because these substances may inactivate the live virus vaccine. A 25 gauge, 5 / 8 [Prime ] 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. 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 virus and other infectious agents from one person to another. Each dose of BIAVAX (rubella and mumps virus vaccine live) II contains not less than the equivalent of 1,000 TCID 50 of the U.S. Reference Rubella Virus and 20,000 TCID 50 of the U.S. Reference Mumps Virus. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. BIAVAX (rubella and mumps virus vaccine live) II, when reconstituted, is clear yellow. HOW SUPPLIED No. 4746 BIAVAX (rubella and mumps virus vaccine live) II is supplied as a single-dose vial of lyophilized vaccine, NDC 0006-4746-00, and a vial of diluent. No. 4669/4309 BIAVAX (rubella and mumps virus vaccine live) II is supplied as follows: (1) a box of 10 single-dose vials of lyophilized vaccine (package A), NDC 0006-4669-00; 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 It is recommended that the vaccine be used as soon as possible after reconstitution. Protect the 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 eight hours. COPYRIGHT © MERCK & CO., INC., 1990

PATIENT INFORMATION No Information Provided.

OVERDOSE No Information Provided. CONTRAINDICATIONS Do not give BIAVAX (rubella and mumps virus vaccine live) 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). History of anaphylactic or anaphylactoid reactions to eggs (see HYPERSENSITIVITY TO EGGS below). 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. HYPERSENSITIVITY TO EGGS Live mumps vaccine is produced in chick embryo cell culture. Persons with a history of anaphylactic, anaphylactoid, or other immediate reactions (e.g., hives, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) subsequent to egg ingestion should not be vaccinated. Evidence indicates that persons are not at increased risk if they have egg allergies that are not anaphylactic or anaphylactoid in nature. Such persons may be vaccinated in the usual manner. There is no evidence to indicate that persons with allergies to chickens or feathers are at increased risk of reaction to the vaccine.

SIDE EFFECTS Burning and/or stinging of short duration at the injection site have been reported. The adverse clinical reactions associated with the use of BIAVAX (rubella and mumps virus vaccine live) II are those expected to follow administration of the monovalent vaccines given separately. These may include malaise, sore throat, cough, rhinitis, headache, dizziness, fever, rash, nausea, vomiting or diarrhea; mild local reactions such as erythema, induration, tenderness and regional lymphadenopathy; parotitis, orchitis, nerve deafness, thrombocytopenia and purpura; allergic reactions such as wheal and flare at the injection site or urticaria; polyneuritis; and arthralgia and/or arthritis (usually transient and rarely chronic). Anaphylaxis and anaphylactoid reactions have been reported. Vasculitis has been reported rarely. Moderate fever [101-102.9°F (38.3-39.4°C)] occurs occasionally, and high fever [above 103°F (39.4°C)] occurs less commonly. On rare occasions, children developing fever may exhibit febrile convulsions. Syncope, particularly at the time of mass vaccination, has been reported. Rash occurs infrequently and is usually minimal, but rarely may be generalized. Erythema multiforme has also been reported rarely. 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 attenuated rubella and mumps virus vaccines given individually indicates that encephalitis and other nervous system reactions have occurred very rarely. These might occur also with BIAVAX (rubella and mumps virus vaccine live) II. Arthralgia and/or arthritis (usually transient and rarely chronic), and polyneuritis are features of natural rubella and vary in frequency and severity with age and sex, being greatest in adult females and least in prepubertal children. This type of involvement as well as myalgia and paresthesia have also been reported following administration of MERUVAX II (Rubella Virus Vaccine Live). 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. DRUG INTERACTIONS No Information Provided.

WARNINGS No Information Provided. PRECAUTIONSGeneral Adequate treatment provisions including epinephrine, should be available for immediate use should an anaphylactic or anaphylactoid reaction occur. 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 3 months following blood or plasma transfusions, or administration of human immune serum globulin. Excretion of small amounts of the live attenuated rubella virus from the nose and 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 rubella vaccine virus to infants via breast milk has been documented (see Nursing Mothers ). There are no reports of transmission of live attenuated mumps virus from vaccinees to susceptible contacts. It has been reported that live attenuated rubella and mumps virus vaccines given individually 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 BIAVAX (rubella and mumps virus vaccine live) II. As for any vaccine, vaccination with BIAVAX (rubella and mumps virus vaccine live) II 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 BIAVAX (rubella and mumps virus vaccine live) II. It is also not known whether BIAVAX (rubella and mumps virus vaccine live) II can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Therefore, the vaccine should not be administered to pregnant females; furthermore, pregnancy should be avoided for three months following vaccination (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: (1) 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; and (2) although mumps virus is capable of infecting the placenta and fetus, there is no good evidence that it causes congenital malformations in humans. Mumps vaccine virus also has been shown to infect the placenta, but the virus has not been isolated from the fetal tissues from susceptible women who were vaccinated and underwent elective abortions. Nursing Mothers It is not known whether mumps vaccine virus is secreted in human milk. 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 BIAVAX (rubella and mumps virus vaccine live) II is administered to a nursing woman.