M-M-R II

M-M-R II

vaccine, mmr

Manufacturer:

MSD

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Measles, mumps and rubella virus vaccine live.
Description
M-M-R II (Measles, Mumps, and Rubella Virus Vaccine Live, MSD) is a live virus vaccine for vaccination against measles (rubeola), mumps and rubella (German measles).
M-M-R II is a sterile lyophilized preparation of (1) Attenuvax (Measles Virus Vaccine Live, MSD), a more attenuated line of measles virus, derived from Enders' attenuated Edmonston strain and propagated in chick embryo cell culture; (2) Mumpsvax (Mumps Virus Vaccine Live, MSD), the Jeryl Lynn (B level) strain of mumps virus propagated in chick embryo cell culture; and (3) Meruvax II (Rubella Virus Vaccine Live, MSD), the Wistar RA 27/3 strain of live attenuated rubella virus propagated in WI-38 human diploid lung fibroblasts.
The reconstituted vaccine is for SC administration. When reconstituted as directed, the dose for injection is 0.5 mL and contains not less than 1000 CCID50 (50% cell culture infectious dose) of measles virus; 12,500 CCID50 of mumps virus; and 1000 CCID50 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), recombinant human albumin (0.3 mg), fetal bovine serum (<1 ppm), other buffer and media ingredients and approximately 25 mcg of neomycin. M-M-R II contains no preservative.
Action
Pharmacology: Measles, mumps and rubella are 3 common childhood diseases, caused by measles virus, mumps virus (paramyxoviruses) and rubella virus (togavirus), respectively, that may be associated with serious complications and/or death. For example, pneumonia and encephalitis are caused by measles. Mumps is associated with aseptic meningitis, deafness and orchitis; and rubella during pregnancy may cause congenital rubella syndrome in the infants of infected mothers.
Clinical studies of 284 triple seronegative children, 11 months to 7 years, demonstrated that M-M-R II is highly immunogenic and generally well tolerated. In these studies, a single injection of the vaccine induced measles hemagglutination-inhibition (HI) antibodies in 95%, mumps neutralizing antibodies in 96% and rubella HI antibodies in 99% of susceptible persons. However, a small percentage (1-5%) of vaccinees may fail to seroconvert after the primary dose.
A study of 6 month old and 15 month old infants born to vaccine-immunized mothers demonstrated that, following vaccination with Attenuvax, 74% of the 6 month old infants developed detectable neutralizing antibody (NT) titers while 100% of the 15 month old infants developed NT. This rate of seroconversion is higher than that previously reported for 6 month old infants born to naturally immune mothers tested by HI assay. When the 6 month old infants of immunized mothers were revaccinated at 15 months, they developed antibody titers equivalent to the 15 month old vaccinees. The lower seroconversion rate in 6 month olds has 2 possible explanations: 1) Due to the limit of the detection level of the assays (NT and enzyme immunoassay [EIA]), the presence of trace amounts of undetectable maternal antibody might interfere with the seroconversion of infants; or 2) the immune system of 6 month olds is not always capable of mounting a response to measles vaccine as measured by the 2 antibody assays.
Efficacy of measles, mumps and rubella vaccines was established in a series of double-blind controlled field trials which demonstrated a high degree of protective efficacy afforded by the individual vaccine components. These studies also established that seroconversion in response to vaccination against measles, mumps and rubella paralleled protection from these diseases.
Following vaccination, antibodies associated with protection can be measured by neutralization assays, HI, or ELISA (enzyme linked immunosorbent assay) tests. Neutralizing and ELISA antibodies to measles, mumps and rubella viruses are still detectable in most individuals 11-13 years after primary vaccination.
Indications/Uses
M-M-R II is indicated for simultaneous vaccination against measles, mumps and rubella in individuals ≥12 months of age (see also Dosage & Administration).
There is some evidence to suggest that infants who are born to mothers who had wild-type measles and who are vaccinated at <1 year of age may not develop sustained antibody levels when later revaccinated. The advantage of early protection must be weighed against the chance for failure to respond adequately on reimmunization.
Infants who are <12 months of age may fail to respond to the measles component of the vaccine due to presence in the circulation of residual measles antibody of maternal origin: The younger the infant, the lower the likelihood of seroconversion. In geographically isolated or other relatively inaccessible populations for whom immunization programs are logistically difficult, and in population groups in which wild-type measles infection may occur in a significant proportion of infants before 15 months of age, it may be desirable to give the vaccine to infants at an earlier age. Infants vaccinated under these conditions at <12 months of age should be revaccinated after reaching 12-15 months.
Dosage/Direction for Use
For SC administration. Do not inject intravascularly.
The dose for any age is 0.5 mL administered SC, preferably into the outer aspect of the upper arm.
Do not give immune globulin (IG) concurrently with M-M-R II Vaccine (see Interactions).
Recommended Vaccination Schedule: Individuals 1st vaccinated at ≥12 months should be revaccinated at 4-6 years since increased risk of exposure typically occurs around elementary school entry. Revaccination is intended to seroconvert those who do not respond to the 1st dose.
(Note: Local vaccination schedules may be substituted for the above recommendations as dictated by local authorities.) Measles Outbreak Schedule: Infants 6-12 months: Local health authorities may recommend measles vaccination of infants between 6-12 months in outbreak situations. This population may fail to respond to the components of the vaccine. Safety and effectiveness of mumps and rubella vaccine in infants <12 months of age have not been established. The younger the infant, the lower the likelihood of seroconversion. Such infants should receive a 2nd dose of M-M-R II at 12-15 months of age followed by revaccination at 4-6 years.
Mumps Outbreak Schedule: Local health authorities may recommend mumps vaccination in a mumps outbreak situation.
Other Vaccination Considerations: 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.
Women of childbearing age should be advised not to become pregnant for 3 months after vaccination and should be informed of the reasons for this precaution (see Use in Pregnancy under Precautions).
If it is practical and if reliable laboratory services are available, women of childbearing age who are potential candidates for vaccination can have serologic tests to determine susceptibility to rubella. However, with the exception of premarital and prenatal screening, routinely performing serologic tests for all women of childbearing age to determine susceptibility (so that vaccine is given only to proven susceptible women) can be effective but is expensive. Also, 2 visits to the health-care provider would be necessary - 1 for screening and 1 for vaccination. Accordingly, rubella vaccination of a woman who is not known to be pregnant and has no history of vaccination is justifiable without serologic testing - and may be preferable, particularly when costs of serology are high and follow-up of identified susceptible women for vaccination is not assured.
Postpubertal females should be informed of the frequent occurrence of generally self-limited arthralgia and/or arthritis beginning 2-4 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 Use in lactation under Precautions).
Other Populations: Previously unvaccinated children >12 months who are in contact with susceptible pregnant women should receive live attenuated rubella vaccine (eg, that contained in monovalent rubella vaccine or in M-M-R II) to reduce the risk of exposure of the pregnant woman.
Individuals planning travel abroad, if not immune, can acquire measles, mumps or rubella and import these diseases to their country. Therefore, prior to international travel, individuals known to be susceptible to one or more of these diseases can receive either a monovalent vaccine (measles, mumps or rubella), or a combination vaccine as appropriate. However, M-M-R II is preferred for persons likely to be susceptible to mumps and rubella; and if monovalent measles vaccine is not readily available, travelers should receive M-M-R II regardless of their immune status to mumps or rubella.
Vaccination has been recommended for susceptible individuals in high-risk groups such as college students, healthcare workers and military personnel.
Post-Exposure Vaccination: Vaccination of individuals exposed to wild-type measles may provide some protection if the vaccine can be administered within 72 hrs of exposure. If, however, vaccine is given a few days before exposure, substantial protection may be afforded. There is no conclusive evidence that vaccination of individuals recently exposed to wild-type mumps or wild-type rubella will provide protection.
Use with Other Vaccines: M-M-R II should be given 1 month before or after administration of other live viral vaccines.
M-M-R II has been administered concurrently with live attenuated varicella and inactivated Haemophilus influenzae type b (Hib) conjugate vaccines using separate injection sites and syringes. No impairment of immune response to individual tested vaccine antigens was demonstrated. The type, frequency, and severity of adverse experiences observed with M-M-R II were similar to those seen when each vaccine was given alone.
Routine administration of DTP (diphtheria, tetanus, pertussis) and/or OPV (oral poliovirus vaccine) concurrently with measles, mumps and rubella vaccines is not recommended because there are limited data relating to the simultaneous administration of these antigens.
However, other schedules have been used. Data from published studies concerning the simultaneous administration of the entire recommended vaccine series (ie, DTaP [or DTwP], IPV [or OPV], Hib with or without hepatitis B vaccine and varicella vaccine), indicate no interference between routinely recommended childhood vaccines (either live, attenuated or killed).
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. If the lyophilized vaccine cannot be dissolved, discard. Withdraw the entire contents into a syringe and inject the total volume of reconstituted vaccine SC.
If the prevention of sporadic measles outbreaks is the sole objective, revaccination with a measles containing vaccine should be considered (see appropriate product circular). If concern also exists about immune status regarding mumps or rubella, revaccination with appropriate mumps- or rubella-containing vaccine should be considered after consulting the appropriate product circulars.
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. 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 M-M-R II vaccine. 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 SC injection.
Overdosage
Overdose has been reported rarely and was not associated with any serious adverse events.
Contraindications
Hypersensitivity to any component of M-M-R II.
Do not give M-M-R II vaccine 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 3 months following vaccination. (See Use in pregnancy under Precautions.)
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 eg, 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. Measles inclusion body encephalitis (MIBE), pneumonitis and death as a direct consequence of disseminated measles vaccine virus infection have been reported in severely immunocompromised individuals inadvertently vaccinated with measles-containing vaccine.
Individuals with a family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.
Special Precautions
General: Adequate treatment provisions including epinephrine injection (1:1000) should be available for immediate use should an anaphylactic or anaphylactoid reaction occur.
Due caution should be employed in administration of M-M-R II to persons with individual or family histories of convulsions, a history of cerebral injury or any other condition in which stress due to fever should be avoided. The physician should be alert to the temperature elevation which may occur following vaccination (see Adverse Reactions).
Hypersensitivity to Eggs: Live measles vaccine and live mumps vaccine are produced in chick embryo cell culture. Persons with a history of anaphylactic, anaphylactoid or other immediate reactions (eg, 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 vaccines containing traces of chick embryo antigen. The potential risk to benefit ratio should be carefully evaluated before considering vaccination in such cases. Such individuals may be vaccinated with extreme caution, having adequate treatment on hand should a reaction occur.
Thrombocytopenia: Individuals with current thrombocytopenia may develop more severe thrombocytopenia following vaccination. In addition, individuals who experienced thrombocytopenia with the 1st dose of M-M-R II (or its component vaccines) may develop thrombocytopenia with repeat doses. Serologic status may be evaluated to determine whether or not additional doses of vaccine are needed. The potential risk to benefit ratio should be carefully evaluated before considering vaccination in such cases (see Adverse Reactions).
Other: Children and young adults who are known to be infected with human immunodeficiency viruses and are not immunosuppressed may be vaccinated. However, the 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).
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 rubella vaccine virus to infants via breast milk has been documented (see Use in lactation).
There are no reports of transmission of live attenuated measles or mumps viruses from vaccinees to susceptible contacts.
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 test is to be done, it should be administered either before or simultaneously with M-M-R II.
Children under treatment for tuberculosis have not experienced exacerbation of the disease when immunized with live measles virus vaccine; no studies have been reported to date of the effect of measles virus vaccines on untreated tuberculous children.
As for any vaccine, vaccination with M-M-R II may not result in protection in 100% of vaccinees.
Use in pregnancy: It is not known whether M-M-R 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 3 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; (2) Mumps infection during the 1st trimester of pregnancy may increase the rate of spontaneous abortion. Although mumps vaccine virus has been shown to infect the placenta and fetus, there is no good evidence that it causes congenital malformations in humans; and (3) Reports have indicated that contracting of wild-type measles during pregnancy enhances fetal risk. Increased rates of spontaneous abortion, stillbirth, congenital defects and prematurity have been observed subsequent to infection with wild-type measles during pregnancy. There are no adequate studies of the attenuated (vaccine) strain of measles virus in pregnancy. However, it would be prudent to assume that the vaccine strain of virus is also capable of inducing adverse fetal effects.
Use in lactation: It is not known whether measles or 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 breastfed infants. In the infants with serological evidence of rubella infection, none exhibited severe disease; however, 1 exhibited mild clinical illness typical of acquired rubella. Caution should be exercised when M-M-R II is administered to a nursing woman.
Use in children: Safety and effectiveness of measles vaccine in infants <6 months have not been established. Safety and effectiveness of mumps and rubella vaccine in infants <12 months have not been established.
Use In Pregnancy & Lactation
Use in pregnancy: It is not known whether M-M-R 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 3 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; (2) Mumps infection during the 1st trimester of pregnancy may increase the rate of spontaneous abortion. Although mumps vaccine virus has been shown to infect the placenta and fetus, there is no good evidence that it causes congenital malformations in humans; and (3) Reports have indicated that contracting of wild-type measles during pregnancy enhances fetal risk. Increased rates of spontaneous abortion, stillbirth, congenital defects and prematurity have been observed subsequent to infection with wild-type measles during pregnancy. There are no adequate studies of the attenuated (vaccine) strain of measles virus in pregnancy. However, it would be prudent to assume that the vaccine strain of virus is also capable of inducing adverse fetal effects.
Use in lactation: It is not known whether measles or 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 breastfed infants. In the infants with serological evidence of rubella infection, none exhibited severe disease; however, 1 exhibited mild clinical illness typical of acquired rubella. Caution should be exercised when M-M-R II is administered to a nursing woman.
Adverse Reactions
The adverse reactions associated with the use of M-M-R II vaccine are those which have been reported following administration of the monovalent or combination vaccines.
Common: Burning and/or stinging of short duration at the injection site.
Occasional: Body as a Whole: Fever (101°F [38.3°C] or higher).
Skin: Rash or measles-like rash usually minimal but may be generalized. Generally, fever, rash or both appear between the 5th and the 12th days.
Rare: Body as a Whole: Mild local reactions eg, erythema, induration and tenderness; sore throat, malaise, atypical measles, syncope, irritability.
Cardiovascular: Vasculitis.
Digestive: Parotitis, nausea, vomiting, diarrhea.
Hematologic/Lymphatic: Regional lymphadenopathy, thrombocytopenia, purpura.
Hypersensitivity: Allergic reactions eg, wheal and flare at injection site, anaphylaxis and anaphylactoid reactions, as well as related phenomena eg, angioneurotic edema (including peripheral or facial edema) and bronchial spasm, urticaria in individuals with or without an allergic history.
Musculoskeletal: Arthralgia and/or arthritis (usually transient and rarely chronic [see following text]), myalgia.
Nervous/Psychiatric: Febrile convulsions in children, afebrile convulsions or seizures, headache, dizziness, paresthesia, polyneuritis, Guillain-Barre syndrome, ataxia, aseptic meningitis (see following text), measles inclusion body encephalitis (MIBE) (see Contraindications).
Encephalitis/encephalopathy have been reported approximately once for every 3 million doses. In no case has it been shown that reactions were actually caused by vaccine. The risk of such serious neurological disorders following live measles virus vaccine administration remains far less than that for encephalitis and encephalopathy with wild-type measles (1/2000 reported cases).
Respiratory System: Pneumonia, pneumonitis (see Contraindications), cough, rhinitis.
Skin: Erythema multiforme, Stevens-Johnson syndrome, vesiculation at injection site, swelling, pruritis.
Special Senses: Forms of optic neuritis, including retrobulbar neuritis, papillitis and retinitis; ocular palsies, otitis media, nerve deafness, conjunctivitis.
Urogenital: Orchitis.
Other: Death from various, and in some cases unknown, causes has been reported rarely following vaccination with measles, mumps and rubella vaccines; however, a causal relationship has not been established in healthy individuals (see Contraindications). No deaths or permanent sequelae were reported in a published post-marketing surveillance study in Finland involving 1.5 million children and adults who were vaccinated with M-M-R II during 1982-1993.
Arthralgia and/or arthritis (usually transient and rarely chronic) and polyneuritis are features of infection with wild-type rubella and vary in frequency and severity with age and sex, being greatest in adult females and least in prepubertal children.
Chronic arthritis has been associated with infection with wild-type 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.
Post-marketing surveillance of the >200 million doses of M-M-R and M-M-R II that have been distributed worldwide over 25 years (1971-1996) indicates that serious adverse events such as encephalitis and encephalopathy continue to be rarely reported.
There have been reports of subacute sclerosing panencephalitis (SSPE) in children who did not have a history of infection with wild-type measles but did receive measles vaccine. Some of these cases may have resulted from unrecognized measles in the 1st year of life or possibly from the measles vaccination. Based on estimated nationwide measles vaccine distribution, the association of SSPE cases to measles vaccination is about 1 case per million vaccine doses distributed. This is far less than the association with infection with wild-type measles, 6-22 cases of SSPE per million cases of measles. The results of a retrospective case-controlled study conducted by the Centers for Disease Control and Prevention suggest that the overall effect of measles vaccine has been to protect against SSPE by preventing measles with its inherent higher risk of SSPE.
Cases of aseptic meningitis have been reported following measles, mumps, and rubella vaccination. Although a causal relationship between the Urabe strain of mumps vaccine and aseptic meningitis has been shown, there is no evidence to link Jeryl Lynn mumps vaccine to aseptic meningitis.
Panniculitis has been reported rarely following administration of measles vaccine.
Drug Interactions
Administration of immune globulins concurrently with M-M-R II may interfere with the expected immune response. Vaccination should be deferred for 3 months or longer following administration of immune globulin (human) and blood or plasma transfusions.
Caution For Usage
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.
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.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Before reconstitution, the lyophilized vaccine is a light yellow compact crystalline plug. M-M-R II, when reconstituted, is clear yellow.
Storage
Store reconstituted vaccine in the vaccine vial in a dark place at 2-8°C (35.6-46.4°F) and discard if not used within 8 hours.
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 of the vaccine. Protect the vaccine from light at all times, since such exposure may inactivate the viruses.
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. Do not freeze the diluent.
Combination pack containing lyophilized vaccine and diluent together should be stored at 2-8°C (36-46°F). It is recommended that the vaccine be used as soon as possible after reconstitution.
ATC Classification
J07BD52 - measles, combinations with mumps and rubella, live attenuated ; Belongs to the class of morbilli viral vaccines.
Presentation/Packing
Vaccine (inj) (vial; single-dose, lyophilized vaccine) 0.5 mL + vial (diluent) x 5's.
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