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Measles Virus Vaccine Live (Monograph)

Drug class: Vaccines
ATC class: J07BJ01
VA class: IM100

Medically reviewed by Drugs.com on Dec 22, 2023. Written by ASHP.

Introduction

Measles virus vaccine live is a preparation of live, attenuated measles virus that stimulates active immunity to measles infection. Measles virus vaccine live is commercially available as a fixed-combination vaccine containing measles, mumps, and rubella antigens (MMR; M-M-R II) and a fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad).

Uses for Measles Virus Vaccine Live

Measles virus vaccine live is used to stimulate active immunity to measles (rubeola). Monovalent measles virus vaccine live (Attenuvax) is no longer commercially available in the US. Measles virus vaccine live is commercially available in the US as a fixed-combination vaccine containing measles, mumps, and rubella antigens (MMR; M-M-R II) for use in adults, adolescents, and children 12 months of age or older and as a fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad) for use in children 12 months through 12 years of age.

The US Public Health Service Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the National Vaccine Advisory Committee (NVAC) recommend universal immunization against measles for all susceptible children, adolescents, and adults, unless measles virus vaccine live is contraindicated. (See Cautions: Precautions and Contraindications.)

Most individuals born before 1957 are likely to have been infected naturally with measles and generally can be considered immune. Individuals born in 1957 or later should be considered immune to measles only if there is documentation of adequate immunization against measles (2 doses of MMR or measles-containing vaccine for school aged-children in grades K-12, college students, health-care personnel, international travelers), natural measles infection diagnosed by a health-care provider, or serologic evidence of measles immunity. Individuals who lack adequate documentation of immunity should be considered susceptible to measles and should be vaccinated, unless measles virus vaccine live is contraindicated. A parental report of measles vaccination, by itself, is not considered adequate documentation of immunization. Clinicians should not provide documentation of immunization for a patient unless they administered the vaccine to the patient or have seen a record documenting vaccination.

Previously, individuals who received a single dose of any live measles virus vaccine when 12 months of age or older were considered to be adequately immunized against measles. In 1989, because of increased measles outbreaks in school-aged children in the US, the ACIP and AAP revised their recommendations to specify that routine primary immunization against measles generally should consist of 2 doses of measles virus vaccine live given at least 1 month (i.e., at least 28 days) apart. This recommendation was made because primary vaccine failure was considered to be a principal contributing factor to these measles outbreaks, and it was further strengthened in 1998 to unequivocally recommend that a 2-dose primary immunization series be completed prior to entry into kindergarten or first grade (i.e., by 4 through 6 years of age).

The ACIP, AAP, AAFP, and NVAC state that MMR is preferred over monovalent measles virus vaccine live (no longer commercially available in the US) for both primary immunization and revaccination to assure immunity to all 3 diseases. Alternatively, in children 12 months through 12 years of age when a dose of MMR and a dose of varicella virus vaccine live are indicated for primary immunization, use of the fixed-combination vaccine containing MMR and varicella virus vaccine live (MMRV; ProQuad) can be considered.

Primary Immunization

Infants and Children 12 Months through 12 Years of Age

For routine primary immunization in children, the ACIP, AAP, and AAFP recommend that the first dose of MMR be given at 12 through 15 months of age. Initiation of immunization with MMR at 12 months of age is recommended for children residing in areas at high risk for measles transmission among preschool-age children, especially large urban areas. (See Infants and Children in High-Risk Areas under Uses: Primary Immunization.) The second dose of MMR preferably should be given at 4 through 6 years of age (just prior to entry into kindergarten or first grade), but may be given earlier during any routine visit provided at least 4 weeks have elapsed since the first dose and both the first and second doses are administered beginning at or after 12 months of age. Those who have not previously received the second MMR dose should complete the schedule by 11–12 years of age (just prior to entry into middle or junior high school). Children who do not have adequate documentation of immunity against measles, mumps, and rubella should be admitted to kindergarten or first grade only after receiving at least one dose of a measles virus-containing vaccine.

The ACIP, AAP, and AAFP state that primary immunization against measles, mumps, and rubella can be integrated with primary immunization against diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib), hepatitis B, influenza, pneumococcal disease, poliomyelitis, and varicella. In general, simultaneous administration (on the same day) of the most widely used vaccines, including diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP), hepatitis B vaccine, Hib conjugate vaccine, MMR, poliovirus vaccine inactivated (IPV), and varicella virus vaccine live, has resulted in seroconversion rates and adverse effects similar to those observed when the vaccines were administered separately. Therefore, the ACIP, AAP, and AAFP recommend simultaneous administration of all vaccines appropriate for the age and previous vaccination status of the recipient, including DTaP, Hib conjugate vaccine, hepatitis B vaccine, influenza vaccine, MMR, IPV, pneumococcal vaccine, and varicella virus vaccine live, especially if an individual is unlikely to return for further vaccination. (See Drug Interactions.)

Infants and Children in High-Risk Areas

During the late 1980s and early 1990s, the incidence of measles in the US increased. At that time, measles outbreaks occurred among unvaccinated preschool-aged children, including those younger than the recommended age for routine vaccination, and also occurred among vaccinated school-aged children. In 1986, 39.2% of measles patients were younger than 5 years of age and children 16 months to 4 years of age accounted for 44.7% of the total preventable cases of measles (i.e., cases in unvaccinated individuals). In 1990, 48.1% of measles patients were younger than 5 years of age; this was the first time since detailed age-related reporting started in 1973 that the proportion of measles cases in this age group exceeded that in school-aged children. In these outbreaks, up to 88% of cases in children 16 months to 4 years of age were unvaccinated. Children in this age group may not yet be enrolled in institutions such as day-care facilities or schools with immunization requirements for enrollment. The ACIP and AAP recommend that increased emphasis be placed on vaccinating preschoolers before they encounter measles in day-care facilities or other environments where young children cluster. In addition, unique measles vaccination strategies may be needed in areas of the US with large numbers of Hispanic individuals who are recent immigrants, preschool-age children, or undocumented residents. Vaccination programs offered at churches and workplaces might reach undocumented residents; however, any strategy should account for the reluctance of such residents to have contact with government agencies.

The ACIP and AAP recommend that all children be vaccinated against measles using a 2-dose regimen of MMR beginning at 12 through 15 months of age in order to achieve maximal seroconversion, unless contraindicated; vaccination of younger children generally has been discouraged because most infants have maternal antibodies that may prevent an adequate immunologic response to the vaccine. In order to improve immunity levels in children younger than 15 months of age living in areas in the US with recurrent measles transmission, the ACIP and AAP recommend that routine measles immunization be initiated at 12 months of age for children residing in areas where the risk of measles is high, especially large urban areas. High-risk areas are defined as counties with more than 5 reported measles cases among preschool-aged children during each of the last 5 years, counties with a recent outbreak among unvaccinated preschool-aged children, or counties with large inner-city urban populations. This recommendation can be implemented for the entire county or only within defined areas of the county. Although there is a slightly lower rate of seroconversion among children vaccinated with a measles virus-containing vaccine at 12–14 months of age than among those vaccinated at 15 months of age or older, the benefit of preventing measles cases among children 12 through 15 months of age is assumed to outweigh the slightly reduced efficacy.

The risk of complications from measles is high among children younger than 12 months of age. Therefore, considering the benefits and risks, the ACIP and AAP recommend that children 6 through 11 months of age be vaccinated against measles when exposure to natural measles is considered likely (e.g., during an outbreak, during international travel). Although monovalent measles virus vaccine live is preferred in such children since benefit from exposure to other antigens included in MMR may be low secondary to persisting maternal antibodies that interfere with seroconversion in this young age group, monovalent measles virus vaccine live is no longer commercially available in the US and MMR should be used when protection against measles is indicated in children 6 through 11 months of age. Regardless of which measles virus-containing vaccine is administered, children vaccinated before 12 months of age have a substantially lower rate of seroconversion than those vaccinated at an older age and should be considered unvaccinated against measles, mumps, and rubella for the purposes of determining the need for further vaccination; such children should be revaccinated with the usual 2-dose regimen of MMR. These children should receive a dose of MMR when they are 12 through 15 months of age (12 months of age for those remaining in a high-risk area) and a second dose at least 1 month (i.e., at least 28 days) later, usually at 4 through 6 years of age (just prior to entry into kindergarten or first grade). The AAP states that, alternatively, immunocompetent infants 6 through 11 months of age who are at high risk of exposure to natural measles virus may be given a dose of immune globulin immediately, and then be given MMR at least 5–6 months after the dose of immune globulin, provided the child is at least 12 months of age. (See Drug Interactions: Immune Globulins.)

Internationally Adopted Children and Other Immigrants

Individuals seeking an immigrant visa for permanent US residency must provide proof of age-appropriate vaccination according to the US Recommended Childhood and Adolescent Immunization Schedule or the US Recommended Adult Schedule. Although this vaccination requirement applies to all immigrant infants and children entering the US, internationally adopted children less than 11 years of age are exempt from the overseas vaccination requirements; however, adoptive parents are required to sign a waiver indicating their intention to comply with the vaccination requirements within 30 days after the infant or child arrives in the US. The CDC states that more than 90% of newly arrived internationally adopted children need catch-up vaccinations to meet the US Recommended Immunization Schedules.

The fact that immunization schedules of other countries may differ from US schedules (e.g., different recommended vaccines, recommended ages of administration, and/or number and timing of vaccine doses) also should be considered. Only written vaccination records should be considered as evidence of previous vaccination since such records are more likely to accurately predict protection if the vaccines administered, intervals between doses, and child’s age at the time of vaccination are similar to US recommendations; however, the extent to which an internationally adopted child’s immunization record reflects their protection against disease is unclear and it is possible there may be transcription errors in such records (e.g., single-antigen vaccine may have been administered although a multiple-antigen vaccine was recorded). Although vaccines with inadequate potency have been produced in other countries, most vaccines used worldwide are immunogenic and produced with adequate quality control standards.

When the immune status of an internationally adopted child is uncertain, health-care providers can either repeat vaccinations (since this usually is safe and avoids the need to obtain and interpret serologic tests) and/or use selective serologic testing to determine the need for immunizations (helps avoid unnecessary injections). The child may have received monovalent measles virus vaccine live in their country of origin, but MMR is not used in most countries. Therefore, although serologic testing is available to verify immunization status in children 12 months of age or older, the CDC states that administration of MMR is preferable to serologic testing unless there is documentation that the child has had mumps and rubella. The ACIP states that the recommended approach is to revaccinate an internationally adopted child with 1 or 2 doses of MMR (depending on the child’s age) without regard to the child’s prior vaccination record since serious adverse effects after MMR vaccination are rare and there is no evidence that administration of MMR increases the risk for adverse reactions among individuals already immune to measles, mumps, or rubella.

Adolescents and Adults

In 1986 and 1990, 10 and 23%, respectively, of measles patients whose ages were reported were 20 years of age or older. During 1990–1994, 47% of reported measles cases occurred in children 10 years of age and older. Measles outbreaks continue to occur at secondary schools, universities and colleges, and other places where young adults congregate. Therefore, the ACIP and AAP state that greater emphasis needs to be placed on vaccinating young adults and recommends that educational institutions require evidence of measles immunity as a criterion for enrollment. The American College Health Association also recommends that colleges and universities implement a prematriculation immunization requirement for measles.

Adolescents 11–12 Years of Age

Because the recommendation for a second dose of MMR was made in 1989, many adolescents born before 1985 (and some born after 1985) may not have received the second vaccine dose. The ACIP, AAP, and AAFP recommend that any adolescent who has not previously received a second dose of MMR receive the dose during a routine preadolescent preventive health-care visit at 11–12 years of age. This routine health-care visit provides an opportunity to administer “catch-up” vaccines that were missed at an earlier age, administer vaccines routinely recommended at 11–12 years of age, administer vaccines recommended for certain high-risk adolescents, schedule future appointments that may be necessary to complete recommended immunization schedules, and provide adolescents with other recommended preventive health services such as guidance on health behaviors and screening for biomedical, behavioral, and emotional conditions. During the health-care visit at 11–12 years of age, the vaccination history of the adolescent should be assessed. If the adolescent does not have information regarding their vaccination history, the healthcare provider should attempt to obtain such information through documentation from the parent, previous providers, or school records. When documentation of an adolescent’s vaccination status is not available at the time of the preventive health-care visit, an assumption can be made that the adolescent has received those vaccines required by state laws and regulations that have been in effect for some time (e.g., those required on entry to kindergarten) and these vaccines can be withheld while awaiting documentation. However, vaccine doses recommended for adolescents that were not included in previous laws and recommendations should be administered.

Ideally, all vaccines routinely indicated at 11–12 years of age should be administered during the initial adolescent visit (MMR, hepatitis B vaccine, tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap), varicella virus vaccine live). However, since multiple doses of some vaccines are required to complete primary immunization and because simultaneous administration of a large number of vaccines may be indicated in some adolescents, providers may need to be flexible in determining which vaccines to administer during the initial visit and which to schedule for return visits. While specific studies evaluating the safety and efficacy of simultaneous administration of vaccines in adolescents are not available, there is extensive evidence from clinical studies and experience in infants and children that simultaneous administration of the most widely used vaccines does not decrease the antibody response or increase adverse reactions to these vaccines. In circumstances where multiple vaccines (i.e., 4 or more) are indicated in adolescents 11–12 years of age, the provider may choose to defer some vaccines for administration during one or more future visits; however, the vaccines should be prioritized based on which require multiple doses, which diseases pose an immediate threat to the adolescent, and whether the adolescent is likely to return for scheduled visits. During any subsequent visits, the adolescent’s vaccination status should be rechecked and any deficiencies corrected.

Adults

Adults who received a measles vaccine in 1968 or later generally do not need to be revaccinated routinely, provided they received the vaccine at 12 months of age or older without concurrent immune globulin; however, such individuals should receive a dose of MMR if they are entering college, beginning employment in a health-care facility, or planning international travel. Some, but not all, studies have demonstrated lower vaccine efficacy and higher attack rates in individuals who received measles vaccine at 12–14 months of age. In 1965–1976, the recommended age for measles vaccination in the US was 12 months of age; therefore, a large proportion of individuals who were 15–26 years of age in 1992 are likely to have been vaccinated when they were 12–14 months of age. The ACIP states that routine revaccination of individuals who received measles vaccine at 12–14 months of age is not recommended, but should be considered during selected measles outbreaks, particularly those in junior and senior high schools.

HIV-infected Individuals

Individuals with human immunodeficiency virus (HIV) infection are at increased risk for severe complications if infected with measles. MMR can be used in HIV-infected children, adolescents, or adults who do not have evidence of severe immunosuppression.

The ACIP, AAP, US Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society, and others state that all asymptomatic HIV-infected children, adolescents, and adults should receive MMR according to the usually recommended immunization schedules. In addition, MMR should be considered for all symptomatic HIV-infected individuals who do not have evidence of severe immunosuppression and who otherwise would be eligible for vaccination. Because the immunologic response to vaccines may decrease as HIV disease progresses, vaccination early in the course of HIV infection may be more likely to induce an immune response; in addition, approximately 5% of HIV-infected infants born in the US will be severely immunocompromised at 12 months of age. Therefore, the ACIP and other experts recommend that HIV-infected infants who are not severely immunocompromised receive MMR as soon as possible upon reaching their first birthday (i.e., at 12 months of age) and consideration should be given to administering the second dose of MMR as soon as 1 month (minimum 28 days) after the first dose rather than waiting until 4 through 6 years of age. If there is an increased risk of exposure to measles, such as during an outbreak, ACIP states that children with HIV infection who are not severely immunosuppressed should receive immunization at an earlier age. At such times, children 6 through 11 months of age should receive MMR and should be revaccinated with MMR as soon as possible upon reaching their first birthday, provided at least 1 month has elapsed since administration of the previous dose of measles virus-containing vaccine, and again as early as 1 month after the second dose but no later than on entry into school.

MMR is contraindicated in HIV-infected individuals with severe immunosuppression (i.e., children younger than 12 months of age with CD4+ T-cell count less than 750/mm3; children 1 through 5 years of age with CD4+ T-cell count less than 500/mm3; children 6 years of age or older, adolescents, and adults with CD4+ T-cell count less than 200/mm3; children younger than 13 years of age with CD4+ T-cell percentage less than 15%). Such individuals should receive immune globulin IM (IGIM) if protection against measles is needed (e.g., in travelers, following exposure to measles). There has been a report of progressive pneumonitis in an individual with advanced acquired immunodeficiency syndrome (AIDS) who received MMR. (See Individuals with Altered Immunocompetence under Cautions: Precautions and Contraindications.)

The serologic response to vaccines (including MMR) may be reduced in some HIV-infected patients and may be inversely correlated with the severity of the disease. AAP and ACIP state that HIV-infected individuals should receive immune globulin IM (IGIM) following exposure to measles, regardless of their prior vaccination status. In addition, the fact that MMR may be ineffective in HIV-infected patients who have received high-dose IV immune globulin therapy (e.g., for the prevention of serious bacterial infections) within the 6 months preceding vaccination should be considered. (See Drug Interactions: Immune Globulins.)

MMR may be given to any family member residing in the household or any other close contact of an HIV-infected patient since extensive experience has shown that live, attenuated MMR vaccine viruses are not transmitted from vaccinated individuals to others.

Health-care Personnel

Health-care personnel are at increased risk for acquiring measles and transmitting the disease to susceptible patients, and the ACIP and the Hospital Infection Control Practices Advisory Committee (HICPAC) recommend that all health-care facilities (i.e., inpatient and outpatient, public and private) ensure that all workers (i.e., medical or nonmedical, paid or volunteer, full- or part-time, student or nonstudent, with or without patient-care responsibilities) have adequate documentation of measles vaccination or immunity (i.e., 2 doses of measles virus-containing vaccine with the first dose given on or after 12 months of age and the second dose given at least 28 days after the first dose, laboratory evidence of immunity, or laboratory confirmation of disease). Facilities that provide care exclusively to geriatric patients who are at minimal risk for measles and complications of the disease are possible exceptions to this recommendation. Health-care workers have a responsibility to avoid transmitting measles to patients and thereby causing them harm.

Although birth before 1957 generally is considered acceptable evidence of measles immunity, health-care facilities should consider recommending 2 doses of MMR to unvaccinated workers born before 1957 who do not have laboratory evidence of measles immunity or laboratory confirmation of disease. Serologic screening prior to measles vaccination is not necessary unless the health-care facility considers it cost-effective.

Travelers

Because the risk of acquiring measles outside the US is greater than the risk incurred in the US and because an increasing proportion of measles cases in the US results from exposure to the disease in foreign countries, the ACIP, AAP, and many clinicians recommend that travelers be immune to measles before leaving the US. Unless a live measles virus-containing vaccine is contraindicated, individuals who travel or reside abroad and who do not have adequate evidence of measles, mumps, and rubella immunity should be vaccinated with MMR.

The optimum age for vaccinating children against measles is 12 through 15 months of age (see Infants and Children under Uses: Primary Immunization) and children 12 months of age or older who will be traveling or residing abroad should receive 2 doses of MMR prior to departure with the doses given 1 month apart (i.e., at least 28 days apart). Children 6 through 11 months of age should receive at least 1 dose of MMR prior to departure. Although monovalent measles virus vaccine live is preferred in those 6 through 11 months of age since the risk of serious disease from mumps or rubella infection is relatively low in infants and benefit from exposure to other antigens included in MMR may be low secondary to persisting maternal antibodies that interfere with seroconversion in this young age group, monovalent measles virus vaccine live is no longer commercially available in the US. Any child who received MMR before 12 months of age should be revaccinated using 2 doses of MMR beginning at 12 through 15 months of age (12 months of age for those remaining in a high-risk area); the second dose of MMR should be given at least 28 days later, usually when the child enters school. Virtually all children younger than 6 months of age are protected against measles because of maternally derived antibodies and usually do not need to receive the vaccine prior to international travel unless the mother is diagnosed with measles.

Postexposure Vaccination

There is some evidence that a measles virus-containing vaccine, if given within 72 hours of exposure to natural measles virus, may provide protection in some cases. Postexposure vaccination also provides future protection to individuals who do not contract the disease. For most susceptible individuals 12 months of age or older who are exposed to measles in most settings (e.g., day-care facilities, schools, colleges, health-care facilities), administration of MMR or other measles virus-containing vaccine within 72 hours of exposure is preferable to using immune globulin IM (IGIM) for postexposure prophylaxis. If MMR is contraindicated (e.g., infants less than 6 months of age, pregnant women, immunocompromised individuals), susceptible individuals may receive an immediate dose of IGIM. For susceptible individuals 6 months of age or older, without contraindications, who are exposed to measles in the home setting, postexposure prophylaxis within 72 hours using the vaccine also is acceptable. However, measles often is not recognized as such until longer than 72 hours has elapsed since initial exposure. Therefore, if more than 72 hours but less than 6 days have elapsed since exposure to natural measles virus, susceptible individuals may receive an immediate dose of IGIM followed by MMR 5–6 months later. Immune globulin should not be given concurrently with a measles virus-containing vaccine. (See Drug Interactions: Immune Globulins.) Any immunity conferred by immune globulin is only temporary unless modified or typical measles occurs despite administration of the globulin.

The use of a measles virus-containing vaccine (MMR) within 72 hours of the exposure is generally preferable to use of immune globulin in individuals 12 months of age or older; immune globulin is principally indicated when the vaccine is contraindicated or more than 72 hours since initial exposure has elapsed. Immune globulin may be especially indicated for susceptible household contacts for whom the risk of complications from measles is high (e.g., contacts who are younger than 12 months of age, pregnant women, immunocompromised individuals). Immune globulin should not be used in an attempt to control measles outbreaks. Severely immunocompromised individuals with HIV infection are at increased risk of serious complications from measles infection and should receive a dose of immune globulin following exposure to measles, regardless of their immunization status. (See HIV-infected Individuals under Uses: Primary Immunization.) Some clinicians administer full replacement doses of immune globulin on a 2- to 4-week schedule to children with AIDS and other clinical manifestations of HIV infection; such therapy may provide protection against measles if the last dose was administered within 3 weeks of the measles exposure.

Outbreak Control

If a measles outbreak occurs in a child-care facility, school (elementary, middle, junior high, senior high), college, university, or other secondary educational institution, the ACIP and AAP recommend that all students (and their siblings) and all school personnel born in 1957 or later be vaccinated against measles, unless they can provide documentation that they received 2 doses of a measles virus-containing vaccine at 12 months of age or older or other evidence of measles immunity. Individuals revaccinated, as well as unvaccinated individuals receiving their first dose of MMR as part of the outbreak control program, may be immediately readmitted to school. Mass revaccination of entire communities is unnecessary. Individuals who have been exempted from measles immunization for medical, religious, or other reasons should be excluded from the outbreak area until at least 2 weeks after the onset of rash in the last case of measles. During measles outbreaks, children as young as 6 months of age also should be vaccinated if exposure to natural measles is considered likely. (See Infants and Children in High-Risk Areas under Uses: Primary Immunization.)

Measles Virus Vaccine Live Dosage and Administration

Reconstitution and Administration

The fixed-combination vaccine containing measles, mumps, and rubella antigens (MMR; M-M-R II) is administered by subcutaneous injection. The vaccine should not be given IV.

MMR is reconstituted by adding the entire amount of diluent supplied by the manufacturer to the vial of lyophilized vaccine and agitating the vial. Only the diluent provided by the manufacturer should be used. The preparation should be discarded if the lyophilized vaccine does not dissolve completely.

Reconstituted MMR should be inspected visually for particulate matter and discoloration prior to administration. The vaccine should be reconstituted and administered using sterile syringes and needles that are free of preservatives, antiseptics, and detergents, since these substances may inactivate live virus vaccines.

To minimize loss of potency and ensure an adequate immunizing dose, MMR should be administered immediately following reconstitution. (See Chemistry and Stability: Stability.)

The preferred site for subcutaneous injection of MMR is the upper-outer triceps area; injections also can be given into the anterolateral thigh. For children 1 year of age and older, adolescents, and adults, the upper-outer triceps area usually is preferred. To ensure appropriate delivery, subcutaneous injections should be made at a 45° angle using a 5/8-inch, 23- to 25-gauge needle.

Since syncope may occur following vaccination, vaccinees should be observed for approximately 15 minutes after the vaccine dose is administered. If syncope occurs, the patient should be observed until symptoms resolve. Syncope after vaccination occurs most frequently in adolescents and young adults.

When multiple vaccines are administered during a single health-care visit, each vaccine should be given with a different syringe and at different injection sites. Injection sites should be separated by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.

Dosage

The usual dose of MMR is 0.5 mL and is the same for all individuals. When reconstituted as specified, each 0.5-mL dose of MMR contains not less than 1000 TCID50 of measles virus, 12,500 TCID50 of mumps virus, and 1000 TCID50 of rubella virus. The entire volume of reconstituted solution in the single-dose vial should be administered.

Infants 6 through 11 Months of Age

When protection against measles is considered necessary (e.g., for outbreak control, for children traveling to or residing in areas outside the US with an increased risk of measles) in infants 6 through 11 months of age, who are considered too young to receive routine primary immunization, a single 0.5-mL dose of MMR should be given. Such children should be considered inadequately immunized and should be revaccinated with the usual 2-dose MMR regimen with the first dose given at 12 through 15 months of age and the second dose usually given prior to elementary school entry (4 through 6 years of age).

Infants and Children 12 Months through 6 Years of Age

For primary immunization against measles in infants and children, a 2-dose regimen of MMR is recommended and the first dose generally is administered at 12 through 15 months of age. For routine childhood immunization, the ACIP, AAP, and AAFP recommend that the first dose of MMR be given at 12 through 15 months of age and the second dose be routinely given at 4 through 6 years of age (just prior to entry into kindergarten or first grade). The second dose may be given earlier during any routine visit, provided at least 4 weeks (i.e., at least 28 days) have elapsed since the first dose and both the first and second doses are administered beginning at or after 12 months of age.

Children who received a dose of monovalent measles virus vaccine live (no longer commercially available in the US) or MMR prior to 12 months of age should be considered inadequately immunized and should be revaccinated with a 2-dose MMR regimen beginning as soon as possible after they reach their first birthday. (See Infants 6 through 11 Months of Age under Dosage and Administration: Dosage.)

Children and Adolescents 7 through 18 Years of Age

A 2-dose regimen is recommended when MMR is indicated in previously unvaccinated children and adolescents 7 through 18 years of age. A preadolescent preventive health-care visit at 11–12 years of age provides an opportunity to complete the 2-dose vaccination series in adolescents who have not previously received the second vaccine dose or to initiate the series in those who have not yet received the vaccine. The minimum interval between doses of MMR should be 4 weeks (i.e., at least 28 days).

Individuals who received monovalent measles virus vaccine live (no longer commercially available in the US) when younger than 12 months of age should be considered susceptible to measles and therefore should be revaccinated with a 2-dose regimen of MMR.

Adults

For adults 19 years of age and older, primary immunization consists of 1 or 2 doses of MMR. The minimum interval between doses is 4 weeks (i.e., at least 28 days).

Cautions for Measles Virus Vaccine Live

Systemic Effects

Serious reactions associated with measles virus vaccine live occur very rarely. Limited data indicate that reactions to the vaccine are not age-related. In addition, adverse reactions following revaccination with the vaccine generally should be expected to occur only among the small proportion of vaccinees who failed to respond to the first dose.

The National Academy of Sciences Institute of Medicine determined that a causal relationship exists between measles, mumps, and rubella virus vaccine live (MMR) vaccination and anaphylaxis, thrombocytopenia, febrile seizures, and acute arthritis. Although vasculitis, otitis media, conjunctivitis, optic neuritis, ocular palsies, Guillain-Barré, and ataxia also have been reported after administration of MMR or its component vaccines and are included in the manufacturers’ labeling, a causal relationship between MMR and these effects has not been established.

Fever and Rash

Moderate fever (38.3–39.4°C) occurs occasionally during the month following vaccination. High fever (39.4°C or higher) has been reported in 5–15% of vaccinees who received monovalent measles virus vaccine live (no longer commercially available in the US). Transient rash also occurs in approximately 5% of vaccinees, is usually minimal, and occurs without generalized distribution. Fever and/or rash, if they occur, generally begin 7–12 and 7–10 days, respectively, following vaccination and are transient, with fever generally persisting for 1–2 days. Most individuals with fever are otherwise asymptomatic. Erythema multiforme, Stevens-Johnson syndrome, and urticaria have been reported rarely.

Seizures

Febrile seizures have occurred rarely in children following administration of measles virus vaccine live, and they can occur in children without known risk factors. Children with a personal or family (i.e., in first-degree family members [siblings or parents]) history of seizures may be at increased risk of seizures following vaccination with measles virus vaccine live; although the precise risk of seizures in such children currently is unknown, it appears to be low. (See Seizures under Cautions: Precautions and Contraindications.) In addition, while children with a personal or family seizure history are at increased risk of developing idiopathic epilepsy, febrile seizures following vaccination do not in themselves increase the probability of subsequent epilepsy or other neurologic disorders.

Most seizures following measles vaccination resemble febrile seizures typical of any agent that can produce fever since they usually are associated with fever, occurring 5–11 days after vaccination when febrile reactions to the vaccine are most common, and are rarely associated with any sequelae. Studies conducted to date have not established an association between measles vaccination and the development of a residual seizure disorder. Rarely, afebrile convulsions and seizures have occurred following administration of measles virus vaccine live.

Antipyretics can prevent febrile seizures associated with measles vaccination if administered before the onset of fever and continued for 5–7 days. However, such antipyretic prophylaxis is difficult because the onset of fever often is sudden and occurs unpredictably. Seizures can occur early in the course of fever. Parents and caregivers should be vigilant for fever that occurs subsequent to vaccination and should be advised regarding appropriate treatment; because of the risk of Reye’s syndrome, aspirin generally should not be used to prevent or control fever among children and adolescents.

Sensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions as well as related phenomena such as angioedema (including peripheral or facial edema) and bronchial spasm, have been reported rarely following administration of MMR in individuals with or without an allergic history. Most hypersensitivity reactions have been minor, consisting of a wheal and flare or urticaria at the injection site. Immediate, anaphylactic reactions to measles virus vaccine live or MMR are extremely rare. Although more than 70 million doses of measles-containing vaccines (MMR) have been distributed in the US since the Vaccine Adverse Events Reporting System (VAERS) was implemented in 1990, only 33 cases of anaphylactic reactions have been reported after MMR vaccination. In addition, only 11 of these cases occurred immediately after vaccination with manifestations consistent with anaphylaxis.

Immediate allergic reactions (i.e., breathing difficulty, hypotension), which may be life threatening, have occurred following administration of monovalent measles virus vaccine live (no longer commercially available in the US) in several children with a history of anaphylactoid reactions to egg ingestion. However, it has been suggested that measles virus vaccine live does not contain enough egg protein to cause a severe reaction in most egg-allergic children, and evidence from recent studies and reports of anaphylactic reactions to the vaccine in individuals who had no evidence of egg allergy suggest that hypersensitivity reactions to the vaccine may be related to some other, as yet undefined, component. Measles virus vaccine live generally has been administered safely to children who had egg allergies that were not anaphylactoid in nature and also has been administered safely to children with a history of immediate reactions to eggs. Some clinicians have suggested that skin testing with MMR be used in children with a history of severe allergic reactions to eggs (e.g., generalized urticaria, shock, manifestations of upper or lower airway obstruction) to identify those who may be at risk for severe reactions to the vaccine and that desensitization procedures be used prior to administration of the vaccine in those with positive skin test results. However, the American Academy of Pediatrics (AAP) and other experts question the predictive value and necessity of such testing since anaphylactic reactions may be unrelated to egg protein and the risk of serious reactions to the vaccine in egg-sensitive individuals appears to be extremely low. (See Allergy to Egg-related Antigens under Cautions: Sensitivity Reactions, in Precautions and Contraindications.)

MMR contains hydrolyzed gelatin as a stabilizer, which rarely may stimulate hypersensitivity reactions in some individuals. An anaphylactic reaction following MMR vaccination has been reported in the US in at least one individual with IgE-mediated anaphylactic sensitivity to gelatin, and similar cases have been reported elsewhere. (See Gelatin Allergy under Cautions: Sensitivity Reactions, in Precautions and Contraindications.)

CNS Effects

A causal relationship has not been definitely established, but a few cases of encephalitis and encephalopathy have been reported rarely after measles vaccination. However, the risk of serious neurologic disorders following vaccination with a measles virus-containing vaccine is considerably less than the risk of encephalitis and encephalopathy associated with wild-type measles infection. Ocular palsies, Guillain-Barré syndrome, measles inclusion body encephalitis (MIBE), aseptic meningitis, seizures, polyneuritis, polyneuropathy, paresthesia, and ataxia have occurred after administration of vaccines containing live, attenuated measles virus.

Rarely, subacute sclerosing panencephalitis (SSPE) has been reported in children who did not have a history of natural measles infection but did receive measles virus vaccine live. Some of these cases may have resulted from unrecognized measles in the first year of life or possibly from the measles vaccination. However, by protecting against natural measles infection, widespread vaccination with measles virus vaccine live has been associated with near elimination of subacute sclerosing panencephalitis overall, indicating that the vaccine substantially reduces the likelihood of developing this encephalitis. Administration of measles virus vaccine live does not increase the risk for developing subacute sclerosing panencephalitis, regardless of whether the vaccinee previously had natural measles infection or has received the vaccine before.

Hematologic Effects

Surveillance of adverse effects in the US and elsewhere indicates that measles virus-containing vaccines (e.g., MMR) rarely can cause clinically evident thrombocytopenia (e.g., purpura) within 2 months after vaccination. In prospective studies, the reported incidence of clinically evident thrombocytopenia after MMR vaccination ranged from 1 per 30,000 to 1 per 40,000 vaccinated children, with a temporal clustering of cases occurring 2–3 weeks after vaccination. With passive surveillance, the reported incidence ranged from 1 per 100,000 to 1 per million distributed doses. Results of one retrospective study confirmed that a causal relation exists between receipt of MMR and idiopathic thrombocytopenic purpura and indicated that the absolute risk within 6 weeks of vaccination was 1 in 22,300 doses with 2 out of 3 cases occurring in the 6-week post-vaccination period being caused by MMR. However, the incidence of thrombocytopenia with natural measles or rubella infection is substantially greater than that with vaccination, being reported as 1 per 3000 children during one measles epidemic. Evidence from case reports suggests that the risk of vaccine-induced thrombocytopenia may be increased in individuals with a history of idiopathic (immune) thrombocytopenic purpura, particularly for those who developed it with a previous dose of the vaccine; however, results of one retrospective study indicate that children with a history of idiopathic thrombocytopenic purpura prior to the first dose of MMR are not at increased risk of vaccine-associated idiopathic thrombocytopenic purpura. In most cases, vaccine-associated thrombocytopenic purpura usually has been transient and benign, although hemorrhage occurred rarely.

Ocular Effects

Ocular palsies generally occurred approximately 3–24 days following measles vaccination; however, a causal relationship has not been definitely established. Forms of optic neuritis, including retrobulbar neuritis, papillitis, and retinitis, occur rarely following viral infections, and have been reported to occur 1–3 weeks following administration of some live virus vaccines.

Other Adverse Systemic Effects

Mild lymphadenopathy is uncommon, and headache, cough, rhinitis, eye pain, generalized malaise, diarrhea, nausea, vomiting, and vasculitis have been reported rarely following measles virus vaccine live. Syncope also has been reported.

Although it has been suggested that administration of measles virus vaccine live is associated with an increased risk of Crohn’s disease, concerns have been raised about the methods used in epidemiologic studies that suggested such an association, and evidence does not support a causal association between the vaccine and risk for Crohn’s or any other inflammatory bowel disease.

Measles inclusion body encephalitis (MIBE), pneumonitis, and death related to disseminated measles vaccine virus infection have been reported in immunocompromised individuals (e.g., those with acquired immunodeficiency syndrome [AIDS]) who received measles-containing vaccines.

Local Effects

Burning and/or stinging of short duration may occur at the injection site because of the slightly acidic pH (6.2–6.6) of the vaccine. Allergic reactions such as wheal and flare at the injection site or urticaria have been reported rarely.

Local reactions characterized by marked swelling, induration, erythema, vesiculation, and edema at the injection site, with or without fever and lymphadenopathy, have occurred following administration of measles virus vaccine live in 4–55% of patients who previously received inactivated measles vaccine. Rarely, more severe reactions that may require hospitalization, including prolonged, high fevers and extensive local reactions, have been reported. These reactions are considerably milder than atypical measles syndrome, an illness which may occur when individuals who previously received inactivated measles vaccine are exposed to natural measles. There is no evidence that individuals who are already immune to measles, either from vaccination with a live measles vaccine or natural disease, are at increased risk of adverse effects following administration of measles virus vaccine live.

Precautions and Contraindications

MMR is contraindicated in individuals who are hypersensitive to the vaccine or any component in the formulation, including gelatin. (See Gelatin Allergy under Cautions: Sensitivity Reactions, in Precautions and Contraindications.) In addition, MMR is contraindicated in those with a history of anaphylactic or anaphylactoid reaction to neomycin. (See Neomycin Allergy under Cautions: Sensitivity Reactions, in Precautions and Contraindications.)

MMR also is contraindicated in certain other individuals. (See Individuals with Altered Immunocompetence under Cautions: Precautions and Contraindications and see Cautions: Pregnancy, Fertility, and Lactation.)

Sensitivity Reactions

Prior to administration, the recipient and/or parent or guardian should be questioned concerning reactions to previous doses of measles virus-containing vaccine or MMR. Individuals who have a hypersensitivity reaction to the first dose of MMR should be tested for immunity to measles; if results indicate immunity, a second dose is not necessary. Any individual with an anaphylactic reaction to a previous dose should not receive another dose, regardless of results of serologic testing.

Epinephrine should be readily available for immediate treatment of an anaphylactic reaction if such a reaction should occur.

Allergy to Egg-related Antigens

MMR is produced in chick embryo cell culture; individuals with a history of anaphylactic, anaphylactoid, or other immediate reaction (e.g., hives, swelling of the mouth or throat, difficulty breathing, hypotension, shock) to egg ingestion may be at increased risk of immediate-type hypersensitivity reactions after receiving vaccines containing traces of chick embryo antigen. The manufacturer states that the potential benefits and risks should be carefully evaluated before considering administration of MMR to individuals with a history of immediate hypersensitivity reactions to egg ingestion, and recommends that such individuals be vaccinated with extreme caution and with adequate treatment readily available should a reaction occur.

The US Public Health Service Advisory Committee on Immunization Practices (ACIP) and others previously recommended that, since MMR is produced in chick embryo fibroblasts, administration of the vaccine in these individuals be deferred until after appropriate skin testing and desensitization procedures had been performed and that the vaccine be administered to these individuals only with extreme caution (in a setting where an immediate allergic reaction can be detected and treated). However, the predictive value and necessity of such testing have been questioned by most experts since measles virus vaccine live has been administered safely to some children with histories of immediate reactions to eggs and most anaphylactic reactions to the vaccine are not associated with egg allergy but to other vaccine components. Therefore, ACIP states that skin testing and use of special protocols are not required when administering a measles virus-containing vaccine in individuals with a history of anaphylactic-like reactions after egg ingestion. A reasonable precaution for individuals with a history of immediate reactions to eggs is to administer MMR in a supervised setting where appropriate emergency treatment material is available.

Evidence indicates that individuals are not at increased risk of hypersensitivity reactions to measles virus-containing vaccine if they have egg allergies that are not anaphylactoid in nature, and administration of MMR to these individuals should follow the usually recommendations. There is no evidence that individuals with allergies to chickens or feathers are at increased risk of allergic reactions to the vaccine.

Neomycin Allergy

Because MMR contain trace amounts of neomycin, the vaccine is contraindicated in individuals who have had an anaphylactic reaction to topically or systemically administered neomycin.

Neomycin allergy usually is characterized by a delayed-type (cell-mediated) hypersensitivity reaction, such as contact dermatitis, rather than an anaphylactic reaction. Following administration of measles virus vaccine live to individuals who have had a delayed-type hypersensitivity reaction to neomycin, the typical adverse reaction, if any, is a contact dermatitis (e.g., an erythematous, pruritic nodule or papule) occurring within 48–96 hours.

The ACIP and the American Academy of Pediatrics (AAP) state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type hypersensitivity reaction to neomycin if benefits of vaccination outweigh risks.

Gelatin Allergy

The possibility of allergic reactions to hydrolyzed gelatin, which is present in MMR as a stabilizer, should be considered since anaphylactic reactions to the vaccine have been reported rarely in individuals with anaphylactic sensitivity to gelatin. MMR should not be administered to individuals with a history of anaphylactic reactions to gelatin or gelatin-containing products. Although skin testing for gelatin sensitivity before administering a gelatin-containing vaccine such as MMR can be considered, there are no specific protocols for this purpose. Because gelatin used in vaccines manufactured in the US usually is derived from porcine sources and food gelatin may be derived solely from bovine sources, a negative food history does not exclude the possibility of a reaction to the gelatin contained in the vaccines.

Individuals with Altered Immunocompetence

MMR generally is contraindicated in individuals with primary immunodeficiencies (e.g., cellular immune deficiency, hypogammaglobulinemia, dysgammaglobulinemia) and in individuals with suppressed immune responses resulting from AIDS or other clinical manifestations of human immunodeficiency virus (HIV) infection, blood dyscrasias, leukemia, lymphomas of any type, or any other malignant neoplasms affecting the bone marrow or lymphatic systems.

Because replication of measles vaccine virus may be potentiated in individuals with primary immunodeficiencies (e.g., cellular immune deficiency, hypogammaglobulinemia, dysgammaglobulinemia) or with suppressed immune response resulting from leukemia, lymphoma, other malignancies affecting the bone marrow or lymphatic system, or blood dyscrasias, concern exists about the potential risk of administering any live virus vaccine to such individuals. Evidence based on case reports has linked measles virus-containing vaccine and measles infection to subsequent death in some severely immunocompromised children. Of the more than 200 million doses of measles virus-containing vaccine administered in the US, fewer than 5 such deaths have been reported. Because of this potentially fatal association, the ACIP states that, with the exception of most HIV-infected individuals, immunocompromised individuals should not receive a measles virus-containing vaccine. MMR should not be given to an individual with a family history of congenital or hereditary immunodeficiency until the immunocompetence of the individual has been documented. There are no case reports linking MMR or other mumps or rubella virus-containing vaccines to clinically important infection caused by the mumps or rubella component in immunocompromised vaccinees.

Severe immunosuppression may be caused by many disease conditions (e.g., congenital immunodeficiency, HIV infection, hematologic or generalized malignancy) and by immunosuppressive therapy. For some conditions, all affected individuals are severely immunocompromised, whereas for other conditions, the degree of immune compromise depends on the severity of the condition, which in turn depends on the disease and treatment stage. MMR generally is contraindicated in individuals receiving immunosuppressive therapy (e.g., corticotropin, corticosteroids [at immunosuppressive dosages], alkylating agents, antimetabolites, radiation therapy), although the manufacturer states that the vaccine is not contraindicated in individuals receiving corticosteroids as replacement therapy (e.g., for Addison’s disease). (See Drug Interactions: Immunosuppressive Agents.) Ultimately, the patient’s clinician must assume responsibility for determining whether the patient is severely immunocompromised based on clinical and laboratory assessment. Measles virus-containing vaccine should not be administered to severely immunocompromised individuals.

The ACIP states that use of live virus vaccines can be considered in patients with leukemia, lymphoma, or other malignancies if the disease is in remission and chemotherapy was terminated at least 3 months prior to vaccination.

Antibody responses to MMR and efficacy may be decreased in immunocompromised individuals.

HIV-infected Individuals

Because of the risk of severe measles in symptomatic HIV-infected individuals and because limited studies and experience with measles, mumps, and rubella immunization in patients with HIV infection have not documented serious or unusual adverse effects, the ACIP, AAP, US Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society, and others state that MMR should be administered to all asymptomatic HIV-infected individuals according to the usually recommended immunization schedules and should be considered for all symptomatic HIV-infected individuals who do not have evidence of severe immunosuppression and who otherwise would be eligible for measles vaccination. The presence of immunocompromised or HIV-infected individuals in a household does not preclude administration of MMR to other household members.

Because of a reported case of progressive pneumonitis in a measles vaccinee who had advanced AIDS and because of other evidence indicating that the antibody response to measles vaccine is diminished in severely immunocompromised individuals, MMR is contraindicated in HIV-infected individuals with severe immunosuppression. (See HIV-Infected Individuals under Uses: Primary Immunization.)

The reported case of pneumonitis occurred in a 20-year-old HIV-infected man with hemophilia A who received a dose of MMR to fulfill a college prematriculation vaccination requirement; a previous dose of measles-containing vaccine had been administered during infancy. At the time of vaccination, the individual was asymptomatic for HIV but immunosuppressed and was not receiving antiretroviral or antipneumocystis therapy. Approximately 13 months after the MMR dose, symptoms of measles pneumonitis developed, and a presumptive diagnosis was made and then confirmed by measles virus culture from a lung biopsy. One month later the patient was rehospitalized for presumptive Mycobacterium avium complex (MAC) disease and then discharged, but subsequently was readmitted and died with a presumptive diagnosis of cytomegalovirus (CMV) encephalitis, with pulmonary measles and MAC as contributing factors; no autopsy was performed. Postmortem testing of the measles virus isolate recovered before the patient’s death showed a high degree of similarity to the Moraten measles virus vaccine strain, and the vaccine strain as the source of the patient’s lung isolate was confirmed.

Fever or Febrile Seizures

Febrile seizures have occurred rarely following administration of a measles virus-containing vaccine. Fever (39.4°C or greater) has been reported. Following administration of MMR, patients should be monitored for temperature elevations.

Caution should be used in individuals with a history of cerebral injury, individual or family history of seizures, or any other condition in which fever-induced stress should be avoided.

Risk of Transmissible Agents in Preparations Containing Albumin

MMR contains recombinant human albumin.

Monovalent measles virus vaccine live (no longer commercially available in the US) and the fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad) contain albumin human. Since albumin human is prepared from pooled human plasma, it is a potential vehicle for transmission of human viruses, and theoretically may carry the risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD).

Concomitant Illness

The decision whether to administer or delay administration of MMR in an individual with a current or recent acute illness depends largely on the severity of symptoms and etiology of the illness. The manufacturer states that MMR is contraindicated in patients with any febrile respiratory illness or other active febrile infections. The ACIP and AAP state that minor acute illness, such as mild upper respiratory infection (with or without fever) or mild diarrhea, usually does not preclude vaccination. However, vaccination of individuals with moderate or severe acute illness (with or without fever) generally should be deferred until they have recovered from the acute phase of the illness. This precaution avoids superimposing adverse effects of the vaccine on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccination. Data generally are not available on the safety and immunogenicity of measles, mumps, and rubella virus-containing vaccines in individuals with moderate or severe febrile illness. Based on preliminary evidence, the possibility that immune response occasionally may be suppressed by concurrent mild upper respiratory infection (possibly secondary to viral infection-induced interferon formation) should be considered when vaccination is undertaken in such individuals; additional study is needed to confirm these findings, but they do not change current recommendations concerning vaccination of individuals with minor concurrent illness.

Thrombocytopenia

Individuals with a history of thrombocytopenic purpura or thrombocytopenia may be at increased risk of developing clinically apparent thrombocytopenia after vaccination. Thrombocytopenia has worsened in those with preexisting thrombocytopenia and may worsen with subsequent doses. The decision to vaccinate such individuals should depend on the benefits of immunity and the risks of recurrence or exacerbation of thrombocytopenia after vaccination or during natural infection with viruses. Although thrombocytopenia can be life-threatening, no deaths have been reported to date as a direct consequence of vaccine-induced thrombocytopenia. Because the benefits of vaccination usually exceed the risks, ACIP states that vaccination with a measles- and/or rubella-containing vaccine is justified in such individuals, particularly considering the even greater risk of thrombocytopenia associated with natural infection with these viruses. However, avoiding a subsequent dose might be prudent if the previous episode of thrombocytopenia occurred in close temporal proximity to (i.e., within 6 weeks after) the previous dose. Serologic evidence of measles immunity may be obtained in lieu of vaccination.

Risk of Neurodevelopmental Disorders

Although it has been theorized that there is a link between the antigens contained in MMR and neurodevelopmental disorders in children (autism), evidence has been insufficient to support an association between neurodevelopmental disorders and MMR. In 2004, the Immunization Safety Review Committee of the Institute of Medicine (IOM) examined the hypothesis that MMR is causally associated with autism and concluded that the evidence favors rejection of a causal relationship between MMR and autism.

Tuberculosis

Vaccination with a measles virus-containing vaccine is not recommended for individuals with untreated, active tuberculosis. Vaccination in these individuals should be deferred until antituberculosis therapy has been initiated. Administration of live, attenuated vaccines is not contraindicated in individuals with a positive tuberculin skin test who do not have active tuberculosis infection. Tuberculin testing is not a prerequisite for administration of MMR.

Transmission of Vaccine Virus

MMR contains live, attenuated virus; there is a theoretical risk that transmission of vaccine virus could occur between vaccinees and susceptible contacts.

Transmission of live, attenuated measles from vaccinees to susceptible contacts has not been reported.

Limitations of Vaccine Effectiveness

MMR may not protect all individuals from measles.

Safety and efficacy of MMR have not been established for postexposure prophylaxis following exposure to measles. (See Uses: Postexposure Vaccination.)

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.

MMR that has been mishandled or has not been stored at the recommended temperature should not be administered. (See Chemistry and Stability: Stability.)

Lyophilized and reconstituted vaccine should be protected from light at all times because exposure to light may inactivate the vaccine virus.

Freezing or exposing the diluent supplied by the manufacturer to freezing temperatures should be avoided; the diluent may be refrigerated or stored at room temperature.

All vaccines should be inspected upon delivery and monitored during storage to ensure that the appropriate temperature is maintained.

Pediatric Precautions

Safety and efficacy of MMR in children younger than 6 months of age have not been established, and use of the vaccine in this age group is not recommended.

Routine immunization against measles is initiated at 12 through 15 months of age. Infants 6 through 11 months of age may receive measles vaccine if protection against measles is considered necessary (e.g., for measles outbreak control, for travelers). Although monovalent measles virus vaccine live is preferred instead of MMR in infants 6 through 11 months of age since the risk of serious disease from mumps or rubella infection is relatively low in infants and benefit from exposure to the mumps or rubella antigens may be low secondary to persisting maternal antibodies that may interfere with seroconversion in this young age group, monovalent measles virus vaccine is no longer commercially available in the US and such infants should receive MMR.

There is some evidence that infants born to mothers who had wild-type measles may not develop sustained antibody levels if vaccinated at less than 12 months of age and later revaccinated.

Geriatric Precautions

Clinical studies of MMR did not include sufficient numbers of seronegative individuals 65 years of age or older to determine whether these individuals respond differently than younger individuals. Other reported clinical experience has not identified differences in responses between geriatric and younger individuals.

Mutagenicity and Carcinogenicity

The mutagenic or carcinogenic potential of MMR have not been evaluated.

Pregnancy, Fertility, and Lactation

Pregnancy

Measles virus-containing vaccine should not be administered to pregnant women, and pregnancy should be avoided for 1–3 months following vaccination with. Although the ACIP and AAP state that measles virus-containing vaccine is contraindicated during pregnancy and that pregnancy should be avoided for 4 weeks after vaccination, the manufacturer states that pregnancy should be avoided for 3 months after vaccination. This precaution is based on the theoretical risk of fetal infection from a live virus vaccine; however, there is no evidence substantiating such risk with measles virus vaccine live.

Natural measles infection during pregnancy increases the risk of spontaneous abortion, stillbirth, congenital defects, and prematurity. Animal reproduction studies have not been performed with MMR. It is not known if the vaccine can cause fetal harm when administered to pregnant women or affect reproductive capacity. There are no adequate studies of the effects of measles virus vaccine live on fetal development; however, there is a theoretical risk of adverse effects for up to 3 months following vaccination. These theoretical risks should be weighed against the risks associated with natural measles infection in unimmunized adolescents or adults.

Reasonable precautions should be taken to preclude vaccination of pregnant women, including asking women if they are pregnant, excluding those who state that they are, and informing the others of the theoretical risks. If a pregnant woman is vaccinated or became pregnant within 1–3 months after vaccination, she should be counseled about the theoretical risks to the fetus; measles, mumps, and/or rubella vaccination during pregnancy should not usually be a reason to consider termination of pregnancy. If exposure to measles occurs during pregnancy, the possibility of providing temporary passive immunity with immune globulin should be considered.

Lactation

It is not known whether MMR is distributed into milk. The manufacturer states that MMR should be administered with caution to nursing women. The ACIP states that breastfeeding generally is not a contraindication to administration of measles virus-containing vaccine since live vaccines appear to pose no special problems for the mother or her nursing infant.

Drug Interactions

Blood Products

Blood products (e.g., whole blood, packed red blood cells, plasma) may interfere with the immune response to certain live virus vaccines, including measles, mumps, and rubella virus vaccine live (MMR; M-M-R II); therefore, MMR should not be administered simultaneously with or for specified intervals before or after administration of blood products.

Administration of MMR should be deferred for at least 3 months following administration of red blood cells (with adenine-saline added); for at least 6 months following administration of packed red blood cells or whole blood; and for at least 7 months following administration of plasma or platelet products.

After receiving MMR, vaccinees should avoid blood products for 2 weeks; if use of a blood product is considered necessary during this period, a repeat vaccine dose should be given after the recommended interval unless serologic testing is feasible and indicates a response to the vaccine was attained.

Immunosuppressive Agents

Individuals receiving immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticotropin, corticosteroids [at immunosuppressive dosages], radiation therapy) may have a diminished response to measles virus-containing vaccine and replication of the virus may be potentiated. Vaccination with MMR should be deferred until the immunosuppressive agent is discontinued; the manufacturer states that individuals receiving corticosteroids as replacement therapy (e.g., those with Addison’s disease) generally may receive the vaccine. The exact interval between discontinuance of immunosuppressive therapy and regaining the ability to respond to live virus vaccines is not known, but live viral vaccines generally should not be administered for at least 3 months after discontinuance of immunosuppressive therapy. Individuals with leukemia in remission who have not received chemotherapy for at least 3 months may receive a live virus vaccine. The precise amount and duration of systemically absorbed corticosteroid therapy needed to suppress the immune system of an otherwise healthy individual are not well defined. Although of recent theoretical concern, there is no evidence of increased severe reactions to live vaccines in individuals receiving corticosteroid aerosol therapy, and such therapy is not in itself a reason to delay vaccination. Most experts, including the US Public Health Service Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics (AAP) agree that short-term (less than 2 weeks), low- to moderate-dose systemic corticosteroid therapy; long-term, alternate-day, systemic corticosteroid therapy using low to moderate doses of short-acting drugs; topical corticosteroid therapy (e.g., nasal, cutaneous, ophthalmic); aerosol corticosteroid therapy; or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive in usual dosages and do not necessarily contraindicate vaccination with live virus vaccines. Although the immunosuppressive effects of corticosteroid therapy vary, many clinicians consider a dose equivalent to 2 mg/kg or 20 mg total of prednisone daily for 2 weeks or longer as sufficiently immunosuppressive to raise concerns about the safety of vaccination with live virus vaccines.

Immune Globulins

Antibodies contained in immune globulin preparations (e.g., immune globulin IM [IGIM], immune globulin IV [IGIV], hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella-zoster immune globulin [VZIG]) may interfere with the immune response to certain live virus vaccines, including measles virus-containing vaccines. The duration of possible interference appears to depend on the dosage of the immune globulin preparation. It was previously suggested that vaccines containing measles virus vaccine live (e.g., MMR) could be administered as early as 6 weeks to 3 months after immune globulin preparations; however, this recommendation was based on data from individuals who received low doses of immune globulin. Recent evidence suggests that high doses of immune globulin preparations can inhibit the immune response to measles virus vaccine live for 3 months or longer.

The ACIP and AAP have made the following recommendations concerning administration of measles virus-containing vaccines in patients who have received immune globulins: MMR should be deferred for at least 3 months following administration of TIG, HBIG, IGIM used for prophylaxis of tetanus, hepatitis B virus (HBV), or hepatitis A virus (HAV); for at least 4 months following administration of RIG; for at least 5 months following administration of VZIG for varicella prophylaxis or IGIM used for measles prophylaxis in immunocompetent individuals; for at least 6 months following use of cytomegalovirus immune globulin IV (CMV-IGIV) or IGIM used for measles prophylaxis in immunocompromised individuals; for at least 8 months following administration of IGIV for replacement therapy of immunodeficiencies or VZIG or IGIV used for postexposure prophylaxis of severe varicella; for at least 8–10 months following administration of IGIV for the treatment of idiopathic thrombocytopenic purpura (ITP); or for at least 11 months following administration of IGIV for Kawasaki syndrome.

If simultaneous administration of a measles virus-containing vaccine and one of these immune globulin preparations or administration at less than the recommended interval is deemed necessary (e.g., because of imminent exposure to disease), the fact that vaccine-induced immunity may be compromised should be considered and, unless there is serologic evidence of an adequate antibody response to the live virus vaccine, an additional dose of vaccine should be administered at the specified interval. If administered simultaneously, the live virus vaccine and immune globulin should be administered at separate sites anatomically remote from one another.

The fact that revaccination may be necessary in individuals who receive an immune globulin preparation shortly after a measles virus-containing vaccine also should be considered. In general, vaccine virus replication and stimulation of immunity occur within 7–14 days after administration of a live virus vaccine. Therefore, if the interval between administration of a measles virus-containing vaccine and subsequent administration of one of these preparations is less than 14 days, an additional dose of vaccine should be given after the appropriate interval previously specified, unless serologic testing indicates that an adequate antibody response to the vaccine occurred. An additional dose of vaccine generally is unnecessary if the interval between vaccination and administration of the immune globulin or blood product is longer than 2 weeks.

Live Vaccines

Measles, Mumps, Rubella, and Varicella Vaccines

Measles virus vaccine live may be administered concurrently with mumps virus vaccine live, rubella virus vaccine live, and varicella virus vaccine live.

Measles virus vaccine live is commercially available in a fixed-combination vaccine containing mumps virus vaccine live and rubella virus vaccine live (MMR) to facilitate concomitant administration of all 3 antigens. Administration of MMR results in immunologic responses similar to those obtained with administration of the 3 antigens at separate sites.

MMR may be administered concurrently with monovalent varicella virus vaccine live (Varivax) at a different site using a separate syringe. Results of studies in healthy children 12–36 months of age indicate that seroconversion rates, antibody responses, and adverse effects reported with simultaneous administration of the vaccines are similar to those reported when the vaccines are administered 6 weeks apart. Because there is a theoretical concern that the immune response to one live viral vaccine may be impaired if administered within 1 month of another, if MMR and varicella virus vaccine live are not administered simultaneously then they should be administered at least 1 month apart. There is some evidence that administration of varicella virus vaccine live less than 30 days after MMR decreases the effectiveness of the varicella vaccine. Results of a retrospective cohort study that used data from the Vaccine Safety Datalink (VSD) project and included children 12 months of age or older who were vaccinated during January 1995 to December 1999 indicate that administration of varicella virus vaccine live less than 30 days after MMR results in a 2.5-fold increase in the incidence of breakthrough varicella infections. However, when the vaccines were administered concurrently, there was no increase in the risk for breakthrough infections.

Measles virus vaccine live also is commercially available in a fixed-combination vaccine containing MMR and varicella virus vaccine live (MMRV; ProQuad). This fixed-combination vaccine is safe and effective in healthy children 12 months through 12 years of age. Studies using MMRV (ProQuad) in healthy children 1–6 years of age indicate that the antibody response to measles, mumps, rubella, and varicella antigens following a single dose of the fixed-combination vaccine are similar to those obtained after a single dose of MMR and a single dose of varicella virus vaccine live (Varivax). However, there is some evidence that the relative risk for febrile seizures in infants may be higher with the fixed-combination vaccine MMRV than that reported when a dose of single-antigen varicella virus vaccine live (Varivax) and a dose of MMR are given concomitantly.

Influenza Vaccine Live Intranasal

Because of theoretical concerns that the immune response to one live virus vaccine might be impaired if given within 30 days of another live virus vaccine, if MMR and influenza virus vaccine live intranasal are not administered on the same day, they should be administered at least 4 weeks apart.

Other Live Vaccines

Some oral live vaccines (e.g., rotavirus vaccine live oral, typhoid vaccine live oral) can be administered concomitantly with or at any interval before or after MMR.

Because of theoretical concerns that the immune response to other live virus vaccines might be impaired if given within 30 days of another live virus vaccine, if MMR and yellow fever vaccine are not administered on the same day, they should be administered at least 4 weeks apart.

Inactivated Vaccines and Toxoids

MMR may be administered concurrently with (using different syringes and different injection sites) or at any interval before or after inactivated vaccines, recombinant vaccines, polysaccharide vaccines, or toxoids.

Haemophilus b Conjugate Vaccines

MMR and Haemophilus influenzae type b (Hib) conjugate vaccines may be given concomitantly at a different site using a separate syringe. Concomitant administration of MMR and Hib vaccine does not interfere with the immune response or increase adverse effects of either vaccine.

Influenza Vaccines

MMR may be given concomitantly with parenteral inactivated influenza vaccines (using different syringes and different injection sites) or at any interval before or after administration of inactivated influenza vaccines.

Pneumococcal Vaccines

MMR may be administered concurrently with pneumococcal vaccine, including pneumococcal conjugate vaccine (PCV) or pneumococcal 23-valent polysaccharide vaccine (PPSV23), at a different site using a separate syringe.

Hepatitis B Vaccine

Although data are limited concerning simultaneous administration of MMR and hepatitis B vaccine, MMR may be administered concomitantly (using different syringes and different injection sites) or at any interval before or after hepatitis B vaccine.

Diphtheria and Tetanus Toxoids and Pertussis Vaccines

Although data are limited concerning simultaneous administration of MMR and diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP), or tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap), MMR may be administered concomitantly (using different syringes and different injection sites) or at any interval before or after DTaP or Tdap.

Laboratory Test Interferences

Tuberculin

Live attenuated measles, mumps, and rubella virus vaccines have been reported to temporarily suppress tuberculin skin sensitivity; therefore, tuberculin tests (if required) should be administered simultaneously with or 4–6 weeks after administration of measles, mumps, and rubella virus vaccine live (MMR; M-M-R II). The US Public Health Service Advisory Committee on Immunization Practices (ACIP) states that simultaneous administration of tuberculin and MMR is the preferred option since this does not interfere with reading the tuberculin test result at 48–72 hours and ensures that the individual has been vaccinated against measles, mumps, and rubella. Although tuberculin testing can be performed and read before administering the vaccine, the ACIP states that this option is the least favored since it will delay vaccination.

Pharmacology

Monovalent measles virus vaccine live (no longer commercially available in the US) and the fixed-combination vaccine containing measles, mumps, and rubella antigens (measles, mumps, and rubella virus vaccine live [MMR; M-M-R II]) stimulate active immunity to measles by inducing production of measles-specific immunoglobulin G (IgG) and M (IgM) antibodies (humoral immunity). Studies using monovalent measles virus vaccine live indicate that the antibody response to initial vaccination (primary response) resembles that caused by primary natural measles infection, with an initial transient increase in serum IgM titers and a subsequent increase in serum IgG titers, although the titers achieved with vaccination are lower. As with natural infection, IgG antibody titers decline slowly over time, but immunity is thought to persist for many years and possibly lifelong in most vaccinees. Individuals who experience initial antigenic stimulation from either natural infection or vaccine generally exhibit an anamnestic (secondary) response to subsequent revaccination or exposure to natural measles. This anamnestic response generally is characterized by a rapid but often transient increase in serum IgG titers but little or no detectable IgM production; however, with more sensitive assays, IgM titers may be detected more frequently, albeit still in low proportion to IgG.

While measurement of measles-specific antibody and assessment of immunity most commonly have been determined using the hemagglutination-inhibition (HI) assay, other more sensitive assays, including enzyme-linked immunosorbent (ELISA), plaque reduction neutralization (PRN), and antihemolysin (AH) assays, are available and being employed. The US Public Health Service Advisory Committee on Immunization Practices (ACIP) states that individuals with serologic evidence of measles-specific antibody, determined by any of the available assays, is considered immune. However, a minimum protective antibody titer has not been established, and some evidence suggests that relatively low titers determined by highly sensitive assays (e.g., PRN titers of 120 or less) may not be protective.

If MMR is administered at 9 months of age or older, a single dose is approximately 85% effective in preventing measles. If MMR is administered at 12 months of age or older, the vaccine is 95% effective after a single dose and 99% effective after 2 doses.

The duration of immunity following vaccination with measles virus-containing vaccine has not yet been established and can only be determined by continued long-term observation. There is serologic and epidemiologic evidence that vaccine-induced immunity to measles persists at least 13–23 years and probably life-long in most vaccinees. Titers of vaccine-induced HI antibodies slowly decline and are lower than those following natural measles infection. However, vaccine failure secondary to waning immunity after initially successful immunization appears to occur in only a small percentage of vaccinees, but evidence of such waning is limited.

Chemistry and Stability

Chemistry

Measles virus vaccine live is a preparation of live, attenuated measles virus. Monovalent measles virus vaccine live (Attenuvax) is no longer commercially available in the US. Measles virus vaccine live is commercially available in the US in a fixed-combination vaccine with mumps virus vaccine live and rubella virus vaccine live (MMR; M-M-R II) and in a fixed-combination vaccine containing MMR and varicella virus vaccine live (MMRV; ProQuad).

Vaccines containing measles virus vaccine live, including MMR, meet standards established by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. Measles virus-containing vaccines commercially available in the US contain the more attenuated Enders’ line of measles virus derived from attenuated Edmonston strain and propagated in chick embryo cell cultures. The potency of MMR is expressed in terms of the amount of virus estimated to infect 50% of a number of standardized tissue culture preparations under specified conditions (Tissue Culture Infective Dose 50% or TCID50). Following reconstitution with the diluent provided by the manufacturer, each 0.5-mL dose of MMR contains not less than 1000 TCID50 of measles virus, 12,500 TCID50 of mumps virus, and 1000 TCID50 of rubella virus. Each 0.5-mL dose of MMR contains sorbitol (14.5 mg), sodium phosphate, sucrose (1.9 mg), sodium chloride, hydrolyzed gelatin (14.5 mg), recombinant albumin human (up to 0.3 mg), fetal bovine serum (less than 1 part per million), and approximately 25 mcg of neomycin. The cells, virus pools, fetal bovine serum, and albumin human used in preparation of MMR are screened for the absence of adventitious agents; the albumin human is processed using the Cohn cold alcohol fractionation procedure.

Lyophilized MMR occurs as a light yellow compact crystalline plug and the reconstituted vaccine occurs as a clear, yellow solution. MMR do not contain thimerosal or any other preservative.

Stability

In lyophilized form, MMR should be refrigerated at 2–8°C but may be frozen. The vials containing diluent provided by the manufacturer may be refrigerated at 2–8°C or stored at room temperature. During shipping, MMR must be stored at 10°C or less and may be packed in solid carbon dioxide (dry ice). If the vaccine is shipped with dry ice, the diluent must be shipped separately.

Following reconstitution with the diluent provided by the manufacturer, MMR should be refrigerated at 2–8°C and discarded if not used within 8 hours. Both the lyophilized and reconstituted vaccine should be protected from light, which may inactivate the virus.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Measles, Mumps, and Rubella Virus Vaccine Live (MMR)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

Measles Virus Vaccine Live (More Attenuated Enders’ Line) 1000 TCID50, Mumps Virus Vaccine Live (Jeryl Lynn [B level] Strain) 12,500 TCID50, and Rubella Virus Vaccine Live (Wistar RA 27/3 Strain) 1000 TCID50 per 0.5 mL

M-M-R II

Merck

Measles, Mumps, Rubella and Varicella Virus Vaccine Live (MMRV)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

Measles Virus Vaccine Live (More Attenuated Enders’ Line) ≥3 log 10 tissue culture infective dose 50% (TCID50), Mumps Virus Vaccine Live (Jeryl Lynn [B level] Strain) ≥4.3 log 10 TCID50, Rubella Virus Vaccine Live (Wistar RA 27/3 Strain) ≥3 log 10 TCID50, and Varicella Virus Vaccine Live (Oka/Merck Strain) ≥3.99 log 10 plaque-forming units (PFU) per 0.5 mL

ProQuad

Merck

AHFS DI Essentials™. © Copyright 2024, Selected Revisions January 1, 2010. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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