M-M-R II

M-M-R II vaccine is a sterile lyophilized preparation of (1) Measles Virus Vaccine Live, an attenuated line of measles virus, derived from Enders' attenuated Edmonston strain and propagated in chick embryo cell culture; (2) Mumps Virus Vaccine Live, the Jeryl Lynn (B level) strain of mumps virus propagated in chick embryo cell culture; and (3) Rubella Virus Vaccine Live, the Wistar RA 27/3 strain of live attenuated rubella virus propagated in WI-38 human diploid lung fibroblasts. The cells, virus pools, recombinant human serum albumin and fetal bovine serum used in manufacturing are tested and determined to be free of adventitious agents.
After reconstitution, each 0.5 mL dose contains not less than 3.0 log₁₀ TCID₅₀ (tissue culture infectious doses) of measles virus; 4.1 log₁₀ TCID₅₀ of mumps virus; and 3.0 log₁₀ TCID₅₀ of rubella virus.
Excipients/Inactive Ingredients: Each dose is calculated to contain sorbitol (14.5 mg), sucrose (1.9 mg), porcine hydrolyzed gelatin (14.5 mg), recombinant human albumin (≤0.3 mg), approximately 25 mcg of neomycin and other buffer and media ingredients. The product contains no preservative.

Pharmacology: Mechanism of Action: M-M-R II vaccination induces antibodies to measles, mumps, and rubella associated with protection which can be measured by neutralization assays, hemagglutination-inhibition (HI) assays, or enzyme linked immunosorbent assay (ELISA) tests. Results from efficacy studies or effectiveness studies that were previously conducted for the component vaccines of M-M-R II were used to define levels of serum antibodies that correlated with protection against measles, mumps, and rubella [see Clinical Studies as follows].
Persistence of Antibody Responses After Vaccination: Neutralizing and ELISA antibodies to measles, mumps, and rubella viruses are still detectable in 95-100%, 74-91%, and 90-100% of individuals respectively, 11 to 13 years after primary vaccination.
Clinical Studies: Clinical Efficacy: Efficacy of measles, mumps, and rubella vaccines was established in a series of double-blind controlled trials. These studies also established that seroconversion in response to vaccination against measles, mumps and rubella paralleled protection.
Immunogenicity: Clinical studies enrolling 284 triple seronegative children, 11 months to 7 years of age, demonstrated that subcutaneously administered M-M-R II vaccine is immunogenic. In these studies, a single subcutaneous injection of the vaccine induced measles HI antibodies in 95%, mumps neutralizing antibodies in 96%, and rubella HI antibodies in 99% of susceptible individuals.
A study of 6-month-old and 15-month-old infants born to mothers vaccinated with a measles vaccine in childhood, demonstrated that, following infant and toddler vaccination subcutaneously with Measles Virus Vaccine, Live (previously US-licensed, manufactured by Merck Sharp & Dohme LLC, Rahway, NJ, USA), 74% of the 6-month-old infants developed detectable neutralizing antibody titers while 100% of the 15-month-old infants vaccinated with Measles Virus Vaccine, Live or M-M-R II vaccine developed neutralizing antibodies. When the 6-month-old infants of immunized mothers were revaccinated at 15 months with M-M-R II vaccine, they developed antibody titers similar to those of toddlers who were vaccinated previously at 15-months of age.
In an open label clinical trial (NCT00432523) 752 children 12 through 18 months of age received M-M-R II either intramuscularly (n=374) or subcutaneously (n=378), concomitantly with VARIVAX. Antibody responses to measles, mumps, and rubella viruses were measured by ELISAs using sera obtained 6 weeks postvaccination. For anti-measles virus, anti-mumps virus and anti-rubella virus, seroresponse rates were defined as the percentage of children seronegative at baseline who achieved antibody titers above the respective seroresponse threshold for each assay 6 weeks post vaccination. Seroresponse thresholds were defined as 255 mIU/mL, 10 EU/mL, and 10 IU/mL for anti-measles virus, anti-mumps virus, and anti-rubella virus antibodies, respectively. For each vaccine antigen at least 89% of enrolled children were seronegative at baseline. In a post hoc analysis, seroresponse rates to mumps and rubella viruses were noninferior for the intramuscular group compared to the subcutaneous group (the lower bound of the 95% confidence interval for the difference in seroresponse rates [intramuscular group minus subcutaneous group] ≥-5%). While the seroresponse rate to measles virus narrowly missed meeting the post hoc criterion of -5% for noninferiority (lower bound of the 95% CI for the difference in seroresponse rate -5.28%), it met the pre-specified criterion using a -10% noninferiority margin. For measles, mumps and rubella antigens the lower bound of the 95% CI of the seroresponse rates was ˃90% after intramuscular administration. The point estimates of the proportions of children achieving antibody titers above the seroresponse thresholds for measles, mumps, and rubella viruses were as follows: 94.3%, 97.7%, and 98.1%, respectively, in the intramuscular group and 96.1%, 98.1%, and 98.1%, respectively, in the subcutaneous group.
Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: M-M-R II vaccine has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility.

M-M-R II is a vaccine indicated for active immunization for the prevention of measles, mumps, and rubella in individuals 12 months of age and older.

For Intramuscular or Subcutaneous administration only.
Dose and Schedule: A single dose of M-M-R II is 0.5 mL.
The first dose is administered at 12 to 15 months of age. A second dose is administered at 4 to 6 years of age.
The second dose may be administered prior to 4 years of age, provided that there is a minimum interval of one month between the doses of measles, mumps and rubella virus vaccine, live.
Children who received an initial dose of measles, mumps and rubella vaccine prior to their first birthday should receive additional doses of vaccine at 12-15 months of age and at 4-6 years of age to complete the vaccination series [see Pharmacology: Clinical Studies: Immunogenicity under Actions].
For post-exposure prophylaxis for measles, administer a dose of M-M-R II vaccine within 72 hours after exposure.
Administration: Sterile Diluent Prefilled Syringe: To reconstitute, use the sterile diluent prefilled syringe supplied with the vaccine since it does not contain preservatives or other antiviral substances which might inactivate the vaccine viruses.
Attach a needle to the prefilled syringe.
Reconstitute the vaccine by slowly injecting the entire volume of sterile diluent contained in the prefilled syringe into the lyophilized vaccine vial. Gently agitate to dissolve completely. Discard if the lyophilized vaccine cannot be dissolved.
If two needles are provided: use one needle to reconstitute the vaccine and the other for its administration to the person to be vaccinated.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Visually inspect the vaccine before and after reconstitution prior to administration. Before reconstitution, the lyophilized vaccine is a light yellow compact crystalline plug. M-M-R II, when reconstituted, is a clear yellow liquid. Do not use the reconstituted vaccine if particulates are present or if it appears discolored.
Withdraw and administer the entire volume of the reconstituted vaccine.
Administer M-M-R II immediately after reconstitution. If not used immediately, the reconstituted vaccine may be stored between 36°F to 46°F (2°C to 8°C), protected from light, for up to 8 hours. Discard reconstituted vaccine if it is not used within 8 hours.

Hypersensitivity: Do not administer M-M-R II vaccine to individuals with a history of hypersensitivity to any component of the vaccine (including gelatin) or who have experienced a hypersensitivity reaction following administration of a previous dose of M-M-R II vaccine or any other measles, mumps and rubella-containing vaccine. Do not administer M-M-R II vaccine to individuals with a history of anaphylaxis to neomycin [see Description].
Immunosuppression: Do not administer M-M-R II vaccine to individuals who are immunodeficient or immunosuppressed due to disease or medical therapy. Measles inclusion body encephalitis (MIBE), pneumonitis and death as a direct consequence of disseminated measles vaccine virus infection have been reported in immunocompromised individuals inadvertently vaccinated with measles-containing vaccine. In this population, disseminated mumps and rubella vaccine virus infection have also been reported.
Moderate or Severe Febrile Illness: Do not administer M-M-R II vaccine to individuals with an active febrile illness with fever >101.3°F (>38.5°C).
Active Untreated Tuberculosis: Do not administer M-M-R II vaccine to individuals with active untreated tuberculosis (TB).
Pregnancy: Do not administer M-M-R II to individuals who are pregnant or who are planning on becoming pregnant within the next month [see Pregnancy under Use in Pregnancy & Lactation; Patient Counselling Information].

Febrile Seizure: There is a risk of fever and associated febrile seizure in the first 2 weeks following immunization with M-M-R II vaccine. For children who have experienced a previous febrile seizure (from any cause) and those with a family history of febrile seizures there is a small increase in risk of febrile seizure following receipt of M-M-R II vaccine [see Adverse Reactions].
Hypersensitivity to Eggs: Individuals 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 may be at an enhanced risk of immediate-type hypersensitivity reactions after receiving M-M-R II vaccine. The potential risks and known benefits should be evaluated before considering vaccination in these individuals.
Thrombocytopenia: Transient thrombocytopenia has been reported within 4-6 weeks following vaccination with measles, mumps and rubella vaccine. Carefully evaluate the potential risk and benefit of vaccination in children with thrombocytopenia or in those who experienced thrombocytopenia after vaccination with a previous dose of measles, mumps, and rubella vaccine [see Adverse Reactions].
Family History of Immunodeficiency: Vaccination should be deferred in individuals with a family history of congenital or hereditary immunodeficiency until the individual's immune status has been evaluated and the individual has been found to be immunocompetent.
Immune Globulins and Transfusions: Immune Globulins (IG) and other blood products should not be given concurrently with M-M-R II [see Immune Globulins and Transfusions under Interactions]. These products may contain antibodies that interfere with vaccine virus replication and decrease the expected immune response.
The Advisory Committee on Immunization Practices (ACIP) has specific recommendations for intervals between administration of antibody containing products and live virus vaccines.
Use in Pregnancy: See Pregnancy under Use in Pregnancy & Lactation.
Use in Lactation: See Lactation under Use in Pregnancy & Lactation.
Use in Children: M-M-R II vaccine is not approved for individuals less than 12 months of age. Safety and effectiveness of measles vaccine in infants below the age of 6 months have not been established [see Pharmacology: Clinical Studies under Actions]. Safety and effectiveness of mumps and rubella vaccine in infants less than 12 months of age have not been established.
Use in the Elderly: Clinical studies of M-M-R II did not include sufficient numbers of seronegative subjects aged 65 and over to determine whether they respond differently from younger subjects.

Pregnancy: Risk Summary: M-M-R II vaccine contains live attenuated measles, mumps and rubella viruses. M-M-R II vaccine is contraindicated for use in pregnant women because infection during pregnancy with the wild-type viruses has been associated with maternal and fetal adverse outcomes.
Increased rates of spontaneous abortion, stillbirth, premature delivery and congenital defects have been observed following infection with wild-type measles during pregnancy. Wild-type mumps infection during the first trimester of pregnancy may increase the rate of spontaneous abortion.
Infection with wild-type rubella during pregnancy can lead to miscarriage or stillbirth. If rubella infection occurs during the first trimester of pregnancy, it can result in severe congenital defects, Congenital Rubella Syndrome (CRS). Congenital Rubella Syndrome in the infant includes, but is not limited to, eye manifestations (cataracts, glaucoma, retinitis), congenital heart defects, hearing loss, microcephaly, and intellectual disabilities. Post-marketing surveillance has identified one case of CRS following inadvertent vaccination of a pregnant woman with a measles, mumps, and rubella virus containing vaccine from an unknown manufacturer. There are no adequate and well-controlled studies of M-M-R II vaccine administration to pregnant women.
All pregnancies have a risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Available data suggest the rates of major birth defects and miscarriage in women who received M-M-R II vaccine within 30 days prior to pregnancy or during pregnancy are consistent with estimated background rates (see Data as follows).
Data: Human Data: A cumulative assessment of post-marketing reports for M-M-R II vaccine from licensure 01 April 1978 through 31 December 2018, identified 796 reports of inadvertent administration of M-M-R II vaccine occurring 30 days before or at any time during pregnancy with known pregnancy outcomes. Of the prospectively followed pregnancies for whom the timing of M-M-R II vaccination was known, 425 women received M-M-R II vaccine during the 30 days prior to conception through the second trimester. The outcomes for these 425 prospectively followed pregnancies included 16 infants with major birth defects, 4 cases of fetal death and 50 cases of miscarriage; no abnormalities compatible with CRS were identified.
The CDC established the Vaccine in Pregnancy registry (1971-1989) of women who had received rubella virus vaccines within 3 months before or after conception. Data on 1221 inadvertently vaccinated pregnant women demonstrated no evidence of an increase in fetal abnormalities or cases of CRS in the enrolled women.
Post-marketing surveillance has identified a case of CRS associated with a rubella virus strain belonging to the genotype that includes the rubella virus strain Wistar RA 27/3 contained in M-M-R II. The infant with CRS was born to a pregnant woman who was inadvertently vaccinated at 5 weeks gestation with a measles, mumps, and rubella virus containing vaccine from an unknown manufacturer.
Mumps vaccine virus has been shown to infect the placenta, but there is no evidence that it causes congenital malformations or disease in the fetus or infant.
Lactation: Risk Summary: It is not known whether measles or mumps vaccine virus is secreted in human milk. Studies have shown that lactating postpartum women vaccinated with live attenuated rubella vaccine may secrete the virus in breast milk and transmit it to breast-fed infants. In the breast-fed infants with serological evidence of rubella virus vaccine strain antibodies, none exhibited severe disease; however, one exhibited mild clinical illness typical of acquired rubella.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for M-M-R II, and any potential adverse effects on the breastfed child from M-M-R II or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

The following adverse reactions include those identified during clinical trials or reported during post-approval use of M-M-R II vaccine or its individual components.
Body as a Whole: Panniculitis; atypical measles; fever; headache; dizziness; malaise; irritability.
Cardiovascular System: Vasculitis.
Digestive System: Pancreatitis; diarrhea; vomiting; parotitis; nausea.
Hematologic and Lymphatic Systems: Thrombocytopenia; purpura; regional lymphadenopathy; leukocytosis.
Immune System: Anaphylaxis, anaphylactoid reactions, angioedema (including peripheral or facial edema) and bronchial spasm.
Musculoskeletal System: Arthritis; arthralgia; myalgia.
Nervous System: Encephalitis; encephalopathy; measles inclusion body encephalitis (MIBE); subacute sclerosing panencephalitis (SSPE); Guillain-Barré Syndrome (GBS); acute disseminated encephalomyelitis (ADEM); transverse myelitis; febrile convulsions; afebrile convulsions or seizures; ataxia; polyneuritis; polyneuropathy; ocular palsies; paresthesia; syncope.
Respiratory System: Pneumonia; pneumonitis; sore throat; cough; rhinitis.
Skin: Stevens-Johnson syndrome; acute hemorrhagic edema of infancy; Henoch-Schönlein purpura; erythema multiforme; urticaria; rash; measles-like rash; pruritus; injection site reactions (pain, erythema, swelling and vesiculation).
Special Senses - Ear: Nerve deafness; otitis media.
Special Senses - Eye: Retinitis; optic neuritis; papillitis; conjunctivitis.
Urogenital System: Epididymitis; orchitis.
In a randomized open-label clinical trial (NCT00432523), conducted in France and Germany, 752 children 12 months through 18 months of age received M-M-R II concomitantly administered with VARIVAX at a separate site, by either the intramuscular (n=374) or subcutaneous (n=378) route. In the overall population, 55.3% were male and the median age was 13.2 months. Local and systemic solicited adverse reactions were recorded by parents or guardians using standardized diary cards. Local solicited reactions were recorded for 4 days after vaccination, and systemic solicited adverse reactions were recorded for 42 days after vaccination. In the event that a participant experienced a rash or a mumps-like illness, parents and/or guardians were instructed to contact the investigator for an examination as soon as possible and no later than 72 hours following onset of symptoms. The nature of any rash was characterized by principal investigator either as measles-like, rubella-like, varicella-like or "other". Study investigators reviewed the diary card with the participant or participant's legal guardian 42 days after vaccination to ensure consistency with protocol definitions. The table presents the frequency of solicited adverse reactions based on the final assessment by the study investigators. (See table.)

Click on icon to see table/diagram/image

Unsolicited adverse events that occurred within 42 days following vaccination were recorded using diary cards supplemented by medical review. Data on unsolicited adverse events were transcribed into the study database during an on-site visit at day 42. The rates and types of reported adverse events (AEs) across groups were similar and included common clinical events that are often reported in the evaluated populations. Serious adverse events occurred at rates of 0.3% and 1% in the intramuscular and subcutaneous groups, respectively. One moderate intensity case of otitis media occurred in a participant in the subcutaneous group was considered related to the study vaccination.

Corticosteroids and Immunosuppressive Drugs: M-M-R II vaccine should not be administered to individuals receiving immunosuppressive therapy, including high dose corticosteroids. Vaccination with M-M-R II vaccine can result in disseminated disease due to measles vaccine in individuals on immunosuppressive drugs [see Immunosuppression under Contraindications].
Immune Globulins and Transfusions: Administration of immune globulins and other blood products concurrently with M-M-R II vaccine may interfere with the expected immune response [see Immune Globulins and Transfusions under Precautions]. The ACIP has specific recommendations for intervals between administration of antibody containing products and live virus vaccines.
Tuberculin Skin Testing: It has been reported that live attenuated measles, mumps and rubella virus vaccines given individually may result in a temporary depression of tuberculin skin sensitivity. Therefore, if a tuberculin skin test with tuberculin purified protein derivative (PPD) is to be done, it should be administered before, simultaneously with, or at least 4 to 6 weeks after vaccination with M-M-R II vaccine.
Use with Other Live Viral Vaccines: M-M-R II vaccine can be administered concurrently with other live viral vaccines. If not given concurrently, M-M-R II vaccine should be given one month before or one month after administration of other live viral vaccines to avoid potential for immune interference.

Vaccine Vial: Exposure to light may inactivate the vaccine viruses.
To maintain potency, M-M-R II must be stored between -50°C and +8°C (-58°F to +46°F). Use of dry ice may subject M-M-R II to temperatures colder than -50°C (-58°F).
Before reconstitution, refrigerate the lyophilized vaccine at 2°C to 8°C (36°F to 46°F).
Sterile Diluent: The sterile diluent should be stored in the refrigerator (2°C to 8°C, 36°F to 46°F) or at room temperature (20°C to 25°C, 68°F to 77°F). Do not freeze the sterile diluent.
Administer M-M-R II vaccine immediately after reconstitution. If not administered immediately, reconstituted vaccine may be stored between 2°C to 8°C (36°F to 46°F), protected from light, for up to 8 hours. Discard reconstituted vaccine if it is not used within 8 hours.

Discuss the following with the patient.
Provide the required vaccine information to the patient, parent, or guardian.
Inform the patient, parent, or guardian of the benefits and risks associated with vaccination.
Question the patient, parent, or guardian about reactions to a previous dose of M-M-R II vaccine or other measles-, mumps-, or rubella-containing vaccines.
Question females of reproductive potential regarding the possibility of pregnancy. Inform female patients to avoid pregnancy for 1 month following vaccination [see Pregnancy under Contraindications; Pregnancy under Use in Pregnancy & Lactation].
Inform the patient, parent, or guardian that vaccination with M-M-R II may not offer 100% protection from measles, mumps, and rubella infection.
Instruct patients, parents, or guardians to report any adverse reactions to their health-care provider.

Vaccines, Antisera & Immunologicals

J07BD52 - measles, combinations with mumps and rubella, live attenuated ; Belongs to the class of morbilli viral vaccines.

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