DESCRIPTION
The vaccine is prepared from the live, attenuated strains of Edmonston-Zagreb measles virus, Leningrad-Zagreb (L-Z) mumps virus and Wistar RA 27/3 rubella virus. The measles and rubella viruses are propagated on human diploid cells (HDC) and the mumps virus is grown on chick fibroblasts from SPF eggs (Specific pathogen free eggs).
The vaccine is lyophilized and is provided with diluent. The product has the appearance of yellowish-white dry cake. The vaccine meets the requirements of WHO when tested by the methods outlined in WHO, TRS 840 (1994).

POTENCY
Each single human dose when reconstituted in a volume of 0.5 ml. contains not less than 1000 CCID₅₀ of measles virus, 5000 CCID₅₀ of mumps virus and 1000 CCID₅₀ of Rubella virus. In addition, the freeze-dried vaccine when stored at 37° C for 7 days shows no loss in potency (less than 1.0 log₁₀ loss in virus titres).

INDICATIONS
For active immunization against measles, mumps and rubella in children from 12 months to 10 years of age. Second dose of MMR is usually advocated any time before the age of 6 years (elementary school entry 4-6 years).In children above 10 years, adolescents and adults, Measles and Rubella (MR) vaccine is recommended. Revaccination may seroconvert primary failures or boost antibody titres of previously vaccinated individuals whose titers have declined. The Advisory Committee on Immunization Practices (ACIP) recommends administration of the first dose of MMR at 12-15 months of age and administration of the second dose of MMR at 4-6 years of age. The vaccine can be safely and effectively given simultaneously with DTP, DT, TT, Td, BCG, Polio vaccine (OPV and IPV), Haemophilus influenzae type b, Hepatitis B, or Yellow fever vaccine or vitamin A supplementation.

APPLICATION AND DOSAGE
The vaccine should be reconstituted only with the entire diluent supplied (Sterile water for injection) using a sterile syringe and needle. With gentle shaking the dried cake is easily dissolved. After reconstitution the vaccine should be used immediately. A single dose of 0.5 ml should be administered by deep subcutaneous injection into the anterolateral aspect of upper thigh in toddlers and upper arm in older children. If the vaccine is not used immediately then it should be stored in the dark at 2-8ºC for no longer than 6 hours.
Any opened container remaining at the end of a session (within six hours of reconstitution) should be discarded.
The vaccine vial monitor (see figure), if present would have been removed on reconstitution.
The diluent supplied is specially designed for use with the vaccine. Only this diluent must be used to reconstitute the vaccine. Do not use diluents from other types of vaccine or for MMR vaccine from other manufacturers. Using an incorrect diluent may result in damage to the vaccine and/or serious reactions to those receiving the vaccine.
Diluent must not be frozen but should be kept cool.
CLOSE ATTENTION SHOULD BE PAID TO THE CONTRAINDICATIONS LISTED
The diluent and reconstituted vaccine should be inspected visually for any foreign particulate matter and / or variation of physical aspects prior to administration. In the event of either being observed, discard the diluent or reconstituted vaccine.

ADVERSE REACTIONS
The type and rate of severe adverse reactions do not differ significantly from the measles, mumps and rubella vaccine reactions described separately.
The measles vaccine may cause within 24 hours of vaccination mild pain and tenderness at the injection site. In most cases, they spontaneously resolve within two to three days without further medical attention. A mild fever can occur in 5-15% of vaccinees 7 to 12 days after vaccination and last for 1-2 days. Rash occurs in approximately 2% of recipients, usually starting 7-10 days after vaccination and lasting 2 days. The mild side effects occur less frequently after the second dose of a measles-containing vaccine and tend to occur only in person not protected by the first dose. Encephalitis has been reported following measles vaccination at a frequency of approximately one case per million doses administered although a causal link is not proven.
The mumps component may result in parotitis and low grade fever. Febrile seizures and orchitis may also occur.
However, moderate fever occurs rarely and aseptic meningitis has been reported very rarely. Vaccine-associated meningitis resolves spontaneously in less than 1 week without any sequelae. The onset of aseptic meningitis is delayed, which may limit the ability to detect these cases by passive surveillance. Vaccine associated aseptic meningitis is observed between 15-35 days post immunization.
The rubella component may commonly result in joint symptoms manifested as arthralgias (25%) and arthritis (10%) among adolescent and adult females that usually last from a few days to 2 weeks. However, such adverse reactions are very rare in children and in men receiving MMR vaccine (0%-3%). Symptoms typically begin 1-3 weeks after vaccination and last 1 day to 2 weeks. These transient reactions seem to occur in non-immunes only, for whom the vaccine is important. Low-grade fever and rash, lymphadenopathy, myalgia and paraesthesiae are commonly reported. Thrombocytopenia is rare and has been reported in less than 1 case per 30 000 doses administered. Anaphylactic reactions are also rare. In susceptible individuals the vaccine may very rarely cause allergic reactions like urticaria, pruritis and allergic rash within 24 hours of vaccination. Clinical experience has exceptionally recorded isolated reactions involving the CNS. These more serious reactions have however, not been directly linked to vaccination.


DRUG INTERACTIONS
Due to the risk of inactivation, the MMR vaccine should not be given within the 6 weeks, and if it is possible the 3 months, after an injection of immunoglobulins or blood product containing immunoglobulins (blood, plasma).
For the same reason, immunoglobulins should not be administered within the two weeks after the vaccination.
Tuberculin positive individuals may transitionally become tuberculin negative after vaccination.

CONTRAINDICATIONS AND WARNINGS
Individuals receiving corticosteroids, other immuno-suppressive drugs or undergoing radiotherapy may not develop an optimal immune response. The vaccine should not be given in febrile states, pregnancy, acute infectious diseases, leukaemia, severe anaemia and other severe diseases of the blood system, severe impairment of the renal function, decompensated heart diseases, following administration of gamma-globulin or blood transfusions or to subjects with potential allergies to vaccine components. The vaccine may contain traces of neomycin. Anaphylactic or anaphylactoid reactions to neomycin, history of anaphylactic or anaphylactoid reactions to eggs (Hypersensitivity to eggs), are absolute contraindications. Low-grade fever, mild respiratory infections or diarrhoea, and other minor illness should not be considered as contraindications. It is particularly important to immunize children with malnutrition.
MMR vaccine should not be administered in pregnant women because of the theoretical but never demonstrated teratogenic risk. Inadvertent receipt of MMR vaccine during pregnancy is not an indication for an abortion. Since MR vaccine is recommended in adults, if pregnancy is planned, then an interval of one month should be observed after MR vaccination. No cases of CRS have been reported in any pregnant women who inadvertently received rubella-containing vaccine in early pregnancy.


IMMUNE DEFICIENCY
Measles, Mumps and Rubella vaccine may be used in children with known or suspected HIV infection. The vaccine is contraindicated in persons who are severely immunocompromised as a result of congenital disease, HIV infection, advanced leukaemia or lymphoma, serious malignant disease, or treatment with high-dose steroids, alkylating agents or anti-metabolites, or in persons who are receiving immunosuppressive therapeutic radiation.


STORAGE
IT IS IMPORTANT TO PROTECT BOTH THE LYOPHILIZED AND RECONSTITUTED VACCINE FROM THE LIGHT. The vaccine should be stored in the dark at a temperature between 2-8°C. For long term storage a temperature of -20°C is recommended for the vaccine. The diluent should not be frozen, but should be kept cool.

SHELF LIFE
24 months from the date of last satisfactory potency test, if stored in a dark place at a temperature between 2-8°C.


PRESENTATION
1 Dose vial plus diluent (0.5ml)
2 Dose vial plus diluent (1 ml)
5 Dose vial plus diluent (2.5 ml)
10 Dose vial plus diluent (5 ml)

THE VACCINE VIAL MONITOR (Optional)

Vaccine Vial Monitors (VVMs) are part of the label on Measles, Mumps and Rubella Vaccine Live Attenuated supplied through Serum Institute of India Ltd. The colour dot which appears on the label of the vial is a VVM. This is a time-temperature sensitive dot that provides an indications of the cumulative heat to which the vial has been exposed. It warns the end user when exposure to heat is likely to have degraded the vaccine beyond an acceptable level.
The interpretation of the VVM is simple. Focus on the central square. Its colour will change progressively. As long as the colour of this square is lighter than the colour of the ring, then the vaccine can be used. As soon as the colour of the central square is the same colour as the ring or of a darker colour than the ring, then the vial should be discarded.