Measles, mumps, and rubella virus vaccine live (MMR) is a fixed-combination preparation containing live attenuated measles, mumps, and rubella viruses.108, 185, 194
Prevention of Measles, Mumps, and Rubella Infection
Measles, mumps, and rubella virus vaccine live (MMR) is used to stimulate active immunity to measles, mumps, and rubella infection in adults and pediatric patients 12 months of age or older.108, 190 There are currently 2 preparations of the MMR vaccine in the US (M-M-R® II and Priorix®).108, 185, 190 The 3 live attenuated viruses contained in both vaccines are genetically similar or identical, and studies have shown similar seroresponse rates and geometric mean antibody concentrations to the measles, mumps, and rubella viruses after the first and second doses of the vaccines; therefore the 2 preparations are considered interchangeable.99, 185, 190 A fixed combination vaccine is also available containing measles, mumps, rubella, and varicella virus vaccine live (MMRV) for use when primary immunization with MMR and varicella vaccine is indicated in pediatric patients 12 months through 12 years of age.99, 194 Previous monovalent vaccines for the measles virus (Attenuvax®), mumps virus (Mumpsvax®), and rubella virus (Meruvax® II) are no longer commercially available in the US.109, 110, 111
Measles, mumps, and rubella are viral infections that can cause potentially serious complications and death.105, 203 Measles is highly contagious and can cause symptoms such as otitis media, pneumonia, and diarrhea, with pneumonia being the most fatal complication.203 Rubella (sometimes called "German measles") is an acute viral disease that mostly affects school-aged children and young adults; serious complications of rubella infection can also occur in pregnant women, including miscarriage, fetal death, or congenital rubella syndrome.115, 118, 203 Mumps mostly affects children and can cause orchitis or more serious complications such as aseptic meningitis and deafness.112, 203 The most effective method of protecting against measles, mumps, and rubella is immunization with the MMR vaccine (or MMRV vaccine in pediatric patients up to 12 years of age).99, 105, 112, 115 Most people who are vaccinated with MMR or MMRV generally will be protected for life against measles and rubella; however, immunity against mumps may decrease over time.99
During the late 1980s and early 1990s, the incidence of measles in the US increased because of low immunization rates in preschool children, particularly in urban areas, and primary vaccine failure (i.e., lack of response to the vaccine) in children who received only 1 dose of the vaccine.105, 116, 124, 145, 196 Implementation of vaccination programs and the addition of a routine second dose of the MMR vaccine for primary vaccination improved vaccine coverage in preschool children and subsequently decreased the incidence of measles to extremely low levels (less than 1 case per 1 million population) in the US to the point where endemic measles was declared eliminated in 2000.99, 105, 106, 124 Following vaccination with 1 dose of MMR, the vaccine is approximately 93% effective against measles, 72% effective against mumps, and 97% effective against rubella; following 2 doses of MMR, the vaccine is 97% effective against measles and 86% effective against mumps.99 In recent years, increasing cases and outbreaks of measles have occurred in many states, the majority of which have been associated with importation of measles by nonvaccinated international travelers to the US from countries where measles is endemic and also with the spread of infection in communities with low measles vaccination rates.124, 106
Although mumps is a common disease in many countries, mumps cases in the US have decreased by more than 99% following implementation of a mumps vaccine program in 1967.112 Rubella disease is no longer endemic in the US, but is common in other parts of the world and can be imported into the US by people who become infected in other countries.118
The CDC's Advisory Committee on Immunization Practices (ACIP) and other experts (e.g., American Academy of Pediatrics [AAP]) provide recommendations for the prevention of measles, mumps, and rubella infection.99, 100, 101, 102, 112, 115, 124 Primary vaccination with a 2-dose series of MMR is recommended in all persons ≥12 months of a the first dose should be administered at 12-15 months of age and the second dose at 4-6 years of age before school entry.99, 102, 104, 105 When MMR and varicella virus vaccine live are indicated for primary immunization in children 12 months through 12 years of age, a 2-dose series using the fixed-combination vaccine containing MMR and varicella virus vaccine live (MMRV; ProQuad®) can be considered; for the first dose in children 12-47 months of age, ACIP recommends that MMR and varicella vaccine be administered separately, but MMRV may be used if parents or caregivers express a preference.99, 193, 194
Vaccination with MMR is also recommended in older children, adolescents, and adults if they do not have evidence of immunity.99, 100 Acceptable evidence of immunity includes at least one of the following: 1) written documentation of adequate vaccination, 2) laboratory evidence of immunity, 3) laboratory confirmation of disease, or 4) birth before 1957.99 Most individuals born before 1957 are likely to have been infected naturally with measles and generally can be considered immune; however, ACIP recommends that healthcare personnel born before 1957 without laboratory evidence of immunity or disease should consider receiving 2 doses of the MMR vaccine.99 For children and adolescents through 18 years of age who were not previously vaccinated with MMR vaccine, ACIP recommends a 2-dose series with the vaccine administered at least 4 weeks apart; alternatively, a 2-dose series with MMRV may be administered (in children through 12 years of age) with a minimum interval between doses of 3 months.102, 124 In adults 19 years of age or older who do not have evidence of immunity to measles, mumps, or rubella, 1 dose of MMR vaccine should be given.100 Adults at high risk for exposure and transmission such as students in postsecondary educational institutions, international travelers, healthcare professionals, and household or close personal contacts of immunocompromised persons who do not have evidence of immunity to measles, mumps, or rubella should complete a 2-dose series with MMR vaccine at least 4 weeks apart if they did not previously receive any doses of MMR; for those who previously received 1 dose of MMR, a second dose should be given to complete the series.100, 105
In healthcare professionals born before 1957 with no evidence of immunity to measles, mumps, or rubella, ACIP states to consider a 2-dose series of MMR vaccine at least 4 weeks apart for protection against measles or mumps, or 1 dose for protection against rubella.100 For healthcare professionals born in 1957 or later, a 2-dose MMR series should be completed at least 4 weeks apart for protection against measles or mumps, or at least 1 dose should be given for protection against rubella.100
The MMR vaccine is contraindicated during pregnancy; however, 1 dose of the vaccine is recommended after pregnancy (before discharge from the healthcare facility) in individuals who do not have evidence of immunity to rubella.100
Individuals with human immunodeficiency virus (HIV) infection are at increased risk for severe complications if infected with measles.108, 170, 171, 207 Vaccination with MMR (2-dose series at least 4 weeks apart) is recommended in HIV-infected children, adolescents, or adults who do not have evidence of immunity to measles, mumps, or rubella and who do not have severe immunosuppression; the vaccine is contraindicated in individuals who are immunodeficient or immunosuppressed due to disease or medical therapy.100, 108, 124, 207 Severe immunosuppression has been defined as a CD4+ T-lymphocyte percentage <15% in individuals ≤5 years of age, and a CD4+ T-lymphocyte percentage <15% or a CD4+ T-lymphocyte count <200 lymphocytes/mm3 in individuals >5 years of age.124
Because an increasing proportion of measles cases in the US results from exposure to the disease in foreign countries, ACIP recommends that all international travelers ≥12 months of age should have documented receipt of 2 appropriately spaced doses of MMR vaccine, andinfants 6-11 months of age† should receive 1 dose of the vaccine prior to travel.106
Both the MMR and MMRV vaccines may be administered at the same time, at different anatomic sites, as other routine childhood vaccines.99, 104, 105, 185 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, haemophilus b (Hib) conjugate vaccine, MMR vaccine, poliovirus vaccine, and varicella virus vaccine live, has resulted in seroconversion rates and adverse effects similar to those observed when the vaccines were administered separately.103, 107 Additional live virus vaccines that are not administered on the same day should be separated by at least 4 weeks.185
MMR vaccine has been used for postexposure prophylaxis in individuals who do not have evidence of immunity.99, 124, 207 Available data suggest that administration of MMR vaccine within 72 hours of exposure to the measles virus will provide protection or lessen disease severity and may also prevent later disease.99, 124, 196 There is no harm in receiving another dose of MMR vaccine if an individual is already immune to measles, mumps, or rubella.99 Postexposure prophylaxis is only indicated in exposed individuals who do not have documented immunity.124 For such individuals 12 months of age or older who are exposed to measles, a dose of MMR vaccine may be indicated depending on the time after initial exposure.124, 207 The use of a measles virus-containing vaccine (MMR) within 72 hours of exposure is generally recommended and immunoglobulin is principally indicated when the vaccine is contraindicated or more than 72 hours since initial exposure has elapsed.124 The American Academy of Pediatrics (AAP) recommends that individuals who are severely immunocompromised who are exposed to measles should receive IV immune globulin (IGIV) prophylaxis (400 mg/kg) after exposure, regardless of their vaccination status.124
MMR vaccine is not effective for posexposure prophylaxis of rubella; however, vaccination after exposure is not harmful and may possibly prevent later disease if re-exposed.111
If a measles outbreak occurs in child-care facilities, schools, colleges, and other institutions of higher education, AAP recommends that all exposed individuals including students (and their siblings) and all school personnel born in 1957 or later be vaccinated against measles, unless they can provide documentation of immunity (i.e., previous vaccination with 2 doses of a measles virus-containing vaccine at 12 months of age or older or other evidence of immunity).124 AAP states that immunization is the intervention of choice for control of measles outbreaks in schools and daycare centers and has been used in children as young as 6 months of age† in previous measles epidemics in the US.124 Individuals who are revaccinated and unvaccinated individuals receiving their first dose of MMR vaccine as part of the outbreak control program may be immediately readmitted to school.124 If an outbreak occurs in a hospital or area served by the hospital, all employees and volunteers who cannot provide evidence of immunity to measles should receive 2 doses of the MMR vaccine and should not have direct patient contact starting on the 5th day after the first exposure to 21 days after the last exposure, regardless of whether they have received vaccine or immune globulin after the exposure.124 Individuals who have been exempted from measles immunization for medical, religious, or other reasons should be excluded from the outbreak area until at least 21 days after the onset of rash in the last case of measles.124 During measles outbreaks, AAP states that children as young as 6 months of age also should be vaccinated if exposure to natural measles is considered likely.124
An additional dose of MMR vaccine may be recommended during a mumps outbreak.99, 101 Outbreaks of mumps primarily have occurred in institutional settings with close contact or in close-knit communities; waning of vaccine immunity over time after receipt of the second dose of MMR vaccine can also contribute to an increased risk of mumps in this setting.101 ACIP recommends that persons previously vaccinated with 2 doses of a mumps-containing vaccine who are identified by public health authorities as being part of a group or population at increased risk of acquiring mumps during an outbreak should receive a third dose of a mumps virus-containing vaccine.101 Public health authorities will notify individuals at increased risk who are candidates for this additional dose.99
Dispensing and Administration Precautions
Fixed-combination vaccines containing measles, mumps, and rubella vaccine live (MMR) are administered by IM injection or subcutaneous injection depending on the preparation.108, 190 There are currently 2 preparations of the MMR vaccine in the US (M-M-R® II and Priorix®).108, 185, 190 A fixed-combination vaccine preparation containing measles, mumps, rubella, and varicella vaccine live (ProQuad®) is also commercially available for use when such vaccines are indicated in children 12 months through 12 years of a consult the prescribing information for ProQuad® for additional details.194
MMR vaccines are supplied as single-dose vials of lyophilized antigen component that must be reconstituted with the accompanying sterile diluent (supplied in a vial or prefilled syringe) prior to administration.108, 190 If the diluent is supplied in a vial, withdraw the entire volume of diluent from the vial and inject into the lyophilized vaccine vial.108 If the diluent is supplied as a prefilled syringe, transfer the entire contents of the prefilled syringe into the vial containing the lyophilized antigen component.108, 190 A single dose of MMR vaccine after reconstitution is approximately 0.5 mL.108, 190 See the manufacturer's prescribing information for additional details on preparation of individual vaccine preparations.108, 190 After reconstitution, withdraw and administer the entire volume immediately.108, 190
The fixed-combination measles, mumps, and rubella vaccine labeled as M-M-R® II is administered by IM or subcutaneous injection.108
Store the lyophilized antigen component at -50 to 8°C prior to use.108 Before reconstitution, store the vaccine at 2-8°C.108 Store the supplied diluent in the refrigerator (2-8°C) or at room temperature (20-25°C); do not freeze.108
Administer immediately after reconstitution.108 If not administered immediately, may store the reconstituted vaccine at 2-8°C for up to 8 hours; protect from light.108
The fixed-combination measles, mumps, and rubella vaccine labeled as Priorix® is administered by subcutaneous injection only.190
Store the lyophilized antigen component at 2-8°C; protect from light.190 Store the supplied diluent syringes in the refrigerator (2-8°C) or at room temperature (up to 25°C).190 Do not freeze the lyophilized antigen component or sterile water diluent.190
Administer immediately after reconstitution.190 If not administered immediately, may store the reconstituted vaccine at 2-8°C for up to 8 hours; do not freeze.190
Prevention of Measles, Mumps, and Rubella Infection (Primary Vaccination)
A single dose of measles, mumps, and rubella virus vaccine live (MMR) is approximately 0.5 mL.108, 190
Infants and Children 12 Months through 6 Years of Age
For primary immunization in infants and children, a 2-dose regimen of MMR vaccine is recommended.99, 102, 105, 108 For routine childhood immunization, the first dose of MMR should be administered at 12-15 months of age and the second dose should be administered at 4 to 6 years of age (prior to school entry).99, 102, 105, 108 The second dose may be given earlier during any routine visit, provided there is a minimum interval of 1 month between the first and second doses.102, 108 Alternatively, a 2-dose series with the fixed combination vaccine containing measles, mumps, rubella, and varicella vaccine live (MMRV) may be used in children 12 months through 6 years of age.194 For the first dose in children 12-47 months of age, ACIP recommends that MMR and varicella vaccine be administered separately, but MMRV may be used if parents or caregivers express a preference.99, 193, 194
Children who received an initial dose of MMR prior to their first birthday should receive additional doses of the vaccine at 12-15 months of age and at 4-6 years of age to complete the vaccination series.108
Children and Adolescents 7 through 18 Years of Age
A 2-dose primary series of MMR is recommended in previously unvaccinated children and adolescents 7 through 18 years of age who do not have evidence of immunity.99 The first and second doses should be administered at least 4 weeks apart; alternatively, a 2-dose series with MMRV may be administered (in children through 12 years of age) with a minimum interval between doses of 3 months.102, 124
For previously unvaccinated adults 19 years of age and older, primary immunization consists of 1 or 2 doses of MMR vaccine.100, 105
In adults who do not have evidence of immunity to measles, mumps, or rubella and are not considered to be a high risk of exposure and transmission, 1 dose of MMR should be given.100
In adults at high risk for exposure and transmission (e.g., students in postsecondary educational institutions, international travelers, healthcare professionals, household or close personal contacts of immunocompromised persons) who do not have evidence of immunity to measles, mumps, or rubella, a 2-dose series with MMR is recommended if they did not previously receive any doses of MMR; for those who previously received 1 dose of MMR, a second dose should be given to complete the series.100, 105 The minimum interval between doses is 4 weeks.100, 105
Most adults born before 1957 are likely to have been infected naturally with measles and generally can be considered immune; however, ACIP recommends that healthcare personnel born before 1957 without laboratory evidence of immunity or disease should consider receiving 2 doses of the MMR vaccine.99
Prevention of Measles, Mumps, and Rubella Infection (Postexposure Prophylaxis)
When used for postexposure prophylaxis of measles in individuals 12 months of age or older, a single dose of MMR should be given within 72 hours of exposure.108
When protection against measles is considered necessary for postexposure prophylaxis in infants 6 through 11 months of age†, who are considered too young to receive routine primary immunization, AAP recommends that a single 0.5-mL dose of MMR be given.124
The manufacturers make no specific dosage recommendations for patients with hepatic impairment.108, 190
The manufacturers make no specific dosage recommendations for patients with renal impairment.108, 190
The manufacturers make no specific dosage recommendations for geriatric patients.108, 190
Febrile seizures have occurred rarely in children following administration of measles-containing virus vaccines.108, 109, 114, 144, 170, 190 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.108, 114, 124, 170
There is some evidence suggesting higher rates of fever and febrile seizures 5 to 12 days after administration of the first dose of the fixed-combination vaccine containing measles, mumps, rubella, and varicella virus live (ProQuad®) in children 12 to 23 months of age who have not been previously vaccinated against measles, mumps, rubella, or varicella, or do not have a history of wild-type infections compared to children vaccinated with a first dose of MMR and monovalent varicella vaccine live as separate injections.104, 194 Exercise caution when administering ProQuad® to persons with an individual or family history of febrile seizures.104, 194
Prior to vaccination, parents and guardians of children with a personal or family history of seizures should be advised of the risk of seizures after measles immunization.124 Children receiving anticonvulsants should continue such therapy after vaccination.124
Allergic or immediate hypersensitivity reactions (e.g., urticaria, angioedema, anaphylaxis) have been reported rarely following vaccination with MMR.108, 190 MMR should not be administered to individuals who have had a severe allergic reaction to a previous dose of measles-containing vaccine or to any vaccine component.124 Appropriate medical treatment used to manage immediate allergic reactions must be available in the event an acute anaphylactic reaction occurs following administration of MMR.190
MMR is produced in chick embryo cell culture;108, 124 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.108, 194 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.108
Immediate allergic reactions (i.e., breathing difficulty, hypotension) 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.109 However, current preparations of measles-containing virus vaccine live do not contain enough egg protein to cause a severe reaction in most egg-allergic children,124, 156, 159, 161, 162, 165 and evidence from studies and reports of anaphylactic reactions to the vaccine in individuals who had no evidence of egg allergy suggest that hypersensitivity reactions may be related to other components.159, 160, 161, 162, 163, 165, 170 Measles virus vaccine live generally has been administered safely to children with egg allergies that were not anaphylactoid in nature and also has been administered safely to children with a history of immediate reactions to eggs.156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 170 The American Academy of Pediatrics (AAP) states that children with egg allergy are at low risk of anaphylactic reactions to measles-containing vaccines (including MMR and MMRV); skin testing for egg allergy is not predictive of such reactions and therefore is not recommended.124 Measles-containing vaccines should not be administered to patients who have had a severe allergic reaction to a previous dose of measles-containing vaccine or to a vaccine component.124
Because MMR (the vaccine labeled as M-M-R® II) contains trace amounts of neomycin, the vaccine is contraindicated in individuals who have had an anaphylactic reaction to neomycin.108 The American Academy of Pediatrics (AAP) states that the MMR vaccine may be used in individuals with a non-anaphylactic neomycin allergy.124
Some preparations of the MMR vaccine (e.g., tip caps of prefilled syringes of diluent supplied with Priorix®) contain natural rubber latex, which may cause allergic reactions.190
Measles virus-containing vaccines (e.g., MMR) rarely can cause clinically evident thrombocytopenia (e.g., purpura) within 2 months after vaccination; the risk of thrombocytopenia is higher after the first dose of the vaccine than after the second dose.108, 124, 170, 175, 176, 177, 178, 179, 181, 182, 190 Carefully evaluate the potential risks and benefits of vaccination in children with thrombocytopenia or in those who experienced thrombocytopenia after vaccination with a previous dose of MMR.108
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.170, 175, 176, 177 With passive surveillance, the reported incidence ranged from 1 per 100,000 to 1 per million distributed doses.170, 178, 179 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.191 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.170, 180 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;170, 179, 181, 182 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.191 In most cases, vaccine-associated thrombocytopenic purpura usually has been transient and benign, resolving within 1 week.170, 179
Individuals with a history of thrombocytopenic purpura or thrombocytopenia may be at increased risk of developing clinically apparent thrombocytopenia after vaccination.108, 170, 179, 181, 182 Thrombocytopenia has worsened in those with preexisting thrombocytopenia and may worsen with subsequent doses.108 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.108
Individuals with Altered Immunocompetence
MMR is contraindicated in individuals who are immunodeficient or immunosuppressed due to disease or medical therapy.108 Immunocompromised patients with disorders associated with increased severity of viral infections should not receive live virus measles vaccine with the exception of people with HIV infection, unless they have evidence of severe immunosuppression.124 Vaccination with MMR should be deferred in individuals with a family history of congenital or hereditary immunodeficiency until the individual's immune status has been evaluated and the individual has been found to be immunocompetent.108
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.170 Evidence based on case reports has linked measles virus-containing vaccine and measles infection to subsequent death in some severely immunocompromised children.170, 171, 183 Of the more than 200 million doses of measles virus-containing vaccine administered in the US, fewer than 5 such deaths have been reported.170
Immune Globulins and Transfusions
Immune globulin and other blood products should not be given concurrently with MMR.108, 124 These products may contain antibodies that interfere with the serologic response to measles vaccines.108, 124 Specific recommendations for intervals between administration of immune globulin or blood products and live virus vaccines are provided in expert guidelines.124
MMR vaccine should be administered at least 2 weeks before planned administration of immune globulin, blood transfusion, or other blood products because of the theoretical possibility that antibody in those products could neutralize vaccine virus and interfere with successful immunization.124 If immune globulin must be administered within 14 days after administration of MMR or MMRV, these vaccines should be administered again after the specified interval.124
Syncope can occur in association with administration of injectable vaccines, including MMR.190
Live attenuated rubella vaccine virus has been detected in the nose and throat of individuals 7 to 28 days after vaccination with a rubella virus-containing vaccine; however, no documented confirmed cases of transmitted rubella vaccine virus have been reported.190
Limitation of Vaccine Effectiveness
Vaccination with MMR may not protect all susceptible individuals from measles, mumps, or rubella infection.190
MMR and MMRV vaccines are contraindicated in pregnant women; infection during pregnancy with the wild-type viruses has been associated with adverse maternal and fetal outcomes such as spontaneous abortion, stillbirth, premature delivery, and congenital defects.108, 190, 194 In pregnant women with no evidence of immunity to rubella, ACIP recommends that a dose of MMR be administered after pregnancy, but before discharge from the healthcare facility.99
It is not known whether measles, mumps, or varicella vaccine virus is secreted in human milk.108, 190, 194 Studies have shown that lactating postpartum women vaccinated with live attenuated rubella vaccine may secrete the virus in breast milk and transmit it to breast-fed infants.108 In breastfed infants with serological evidence of rubella virus vaccine strain antibodies, none exhibited severe disease; however, one infant exhibited mild clinical illness typical of acquired rubella.108
ACIP states that it is safe for breastfeeding women to receive MMR vaccination.99 Breastfeeding does not interfere with the response to MMR vaccine and the nursing infant will not be affected by vaccine present in breastmilk.99
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for these vaccines, and any potential adverse effects on the breastfed child from the vaccine or from the underlying maternal condition.108, 190 For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.108, 190
Measles, mumps, and rubella virus vaccine live is not approved for use in individuals less than 12 months of a however, the vaccine has been used for postexposure prophylaxis and outbreak control in infants as young as 6 months of age†.108, 124, 190 Safety and efficacy of MMR in infants younger than 6 months of age have not been established.108, 190
Clinical studies of MMR did not include sufficient numbers of individuals 65 years of age or older to determine whether these individuals respond differently than younger individuals.108, 190
Common adverse effects reported in individuals receiving M-M-R® II: injection site reactions (erythema, pain, and swelling), fever.108
Common adverse effects reported in individuals 12 through 15 months of age receiving Priorix®: local reactions including pain and redness, and systemic reactions including irritability, loss of appetite, drowsiness, and fever.190
Common adverse effects reported in individuals 4 through 6 years of age receiving Priorix®: local reactions including pain, redness, and swelling, and systemic reactions including loss of appetite, drowsiness, and fever.190
Common adverse effects reported in individuals 7 years of age and older receiving Priorix®: local reactions including pain and redness.190
Corticosteroids and Immununosuppressive Drugs
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.108 The American Academy of Pediatrics (AAP) states that for patients who have received high doses of corticosteroids (≥2 mg/kg of body weight or ≥20 mg/day of prednisone or its equivalent for people who weigh ≥10 kg) for 14 days or more and who otherwise are not immunocompromised, the recommended interval between stopping the corticosteroids and immunization is at least 4 weeks.124 In general, inhaled steroids do not cause immunosuppression and are not a contraindication to immunization.124
Immune Globulins and Blood Products
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.108, 124, 170 Similarly, blood products (e.g., whole blood, packed red blood cells, plasma) may interfere with the immune response to certain live virus vaccines, including MMR; therefore, MMR should not be administered simultaneously with or for specified intervals before or after administration of blood products.124
Specific recommendations for intervals between administration of immune globulin or blood products and live virus vaccines are provided in expert guidelines.124 MMR vaccine should be administered at least 2 weeks before planned administration of immune globulin, blood transfusion, or other blood products because of the theoretical possibility that antibody in those products could neutralize vaccine virus and interfere with successful immunization.124 If immune globulin must be administered within 14 days after administration of MMR or MMRV, these vaccines should be administered again after the specified interval.124
MMR vaccines may interfere with results of tuberculin skin testing by suppressing tuberculin skin test reactivity and also possibly affect testing with interferon gamma release assay (IGRA).108, 124 If a tuberculin skin test with tuberculin purified protein derivative (PPD) is necessary, the test should be performed before, simultaneously with, or at least 4 to 6 weeks after vaccination with MMR.108
Both the MMR and MMRV vaccines may be administered at the same time, at different anatomic sites, as other routine nonlive or live attenuated childhood vaccines.99, 108, 135, 185 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, and varicella virus vaccine live, has resulted in seroconversion rates and adverse effects similar to those observed when the vaccines were administered separately.103, 107 Additional live virus vaccines that are not administered simultaneously (on the same day) should be separated by at least 4 weeks to avoid the potential for immune interference.108, 135, 185
MMR may be administered concurrently with monovalent varicella virus vaccine live (Varivax®) at a different site using a separate syringe.103, 107, 108, 124, 209 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.209 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.103, 124 There is some evidence that administration of varicella virus vaccine live less than 30 days after MMR decreases the effectiveness of the varicella vaccine.103 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.103 However, when the vaccines were administered concurrently, there was no increase in the risk for breakthrough infections.103 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®).194, 195 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.194
In a study evaluating the antibody responses to the measles, mumps, and rubella virus vaccine live in children 12-15 years of age who received either the M-M-R® II or Priorix® preparations of the vaccine, all study participants also received Havrix® (hepatitis A virus vaccine) and Varivax® (varicella virus vaccine).190 Children enrolled in the US also received a pneumococcal conjugate vaccine (Prevnar®) concomitantly.190 There was no evidence of interference with the antibody responses to these vaccines when administered concomitantly.190
In a study evaluating the antibody responses to the measles, mumps, and rubella virus vaccine live in children 4-6 years of age who received either the M-M-R® II or Priorix® preparations of the vaccine, a subset of study participants also received Kinrix® (diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine) and Varivax® (varicella virus vaccine).190 There was no evidence of interference with the antibody responses to these vaccines when administered concomitantly.190
The fixed-combination vaccine containing measles, mumps, and rubella antigens (measles, mumps, and rubella virus vaccine live [MMR; M-M-R® II]) stimulates active immunity to measles by inducing production of measles-specific immunoglobulin G (IgG) and M (IgM) antibodies (humoral immunity) and also induces a cell-mediated immune response.108, 196 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,136, 137 although the titers achieved with vaccination are lower. As with natural infection, IgG antibody titers decline slowly over time,113, 117, 136 but immunity is thought to persist for many years and possibly lifelong in most vaccinees.113, 136 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.136, 138, 139 This anamnestic response generally is characterized by a rapid but often transient increase in serum IgG titers but little or no detectable IgM production;136, 138, 139 however, with more sensitive assays, IgM titers may be detected more frequently, albeit still in low proportion to IgG.138
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.108 There is serologic and epidemiologic evidence that vaccine-induced immunity to measles persists at least 13-23 years.113, 136 and probably life-long in most vaccinees.136 Titers of vaccine-induced antibodies as measured by the hemagglutination-inhibition (HI) assay have been shown to slowly decline and are lower than those following natural measles infection.113, 117
The rubella vaccine component induces both humoral and cellular immunity; studies indicate that 1 dose of the vaccine can provide long lasting immunity.105 Although antibodies induced by the rubella vaccine may decrease over time, data suggest that waning immunity with increasing susceptibility to rubella disease does not occur.105
The mumps vaccine component produces a subclinical, noncommunicable infection with few adverse effects, probably involving both the humoral and cellular immune responses.105
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for intramuscular or subcutaneous use | No less than 3.0 log10 Tissue Culture Infective Dose (TCID)50of measles virus live (Enders' attenuated Edmonston strain), 4.1 log10 TCID50of mumps virus live (Jeryl Lynn live attenuated strain), and 3.0 log10 TCID50of rubella virus live (Wistar RA 27/3 live attenuated strain) per 0.5 mL dose after reconstitution | M-M-R® II (supplied with sterile diluent in a vial or prefilled syringe) | Merck Sharp and Dohme |
Suspension, for subcutaneous injection | No less than 3.4 log10 Cell Culture Infective Dose 50% (CCID50) of measles virus live (Schwarz live attenuated strain), 4.2 log10 CCID50of mumps virus live (RIT 4385 live attenuated strain derived from Jeryl Lynn strain), and 3.3 log10 CCID50of rubella virus live (Wistar RA 27/3 live attenuated strain) per 0.5 mL dose after reconstitution | Priorix® | GlaxoSmithKline |
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 |
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