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

Brand names: M-M-R II, Priorix
Drug class: Vaccines

Introduction

Measles, mumps, and rubella virus vaccine live (MMR) is a fixed-combination preparation containing live attenuated measles, mumps, and rubella viruses.^{108 185 190}

Uses for Measles, Mumps, and Rubella Virus Vaccine Live

Prevention of Measles, Mumps, and Rubella Infection

Used to stimulate active immunity to measles, mumps, and rubella infection in adults and pediatric patients ≥12 months of age.^{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; therefore the 2 preparations are considered interchangeable.^{108 185 190}

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 vaccine preparations for measles virus (Attenuvax), mumps virus (Mumpsvax), and rubella virus (Meruvax II) are no longer commercially available in the US.^{109 110 111}

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.^{99 100 101 102 112 115 124}

Primary vaccination with a 2-dose series of MMR is recommended in all persons ≥12 months of age; 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, may consider a 2-dose series using the fixed-combination vaccine containing MMR and varicella virus vaccine live (MMRV; ProQuad); 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}

For children and adolescents through 18 years of age who were not previously vaccinated with MMR, ACIP recommends a 2-dose series with MMR 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 who do not have evidence of immunity to measles, mumps, or rubella, 1 dose of MMR should be given.¹⁰⁰

In adults ≥19 years of age with 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 should be administered at least 4 weeks apart if no previous doses of MMR were given; 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 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

MMR vaccine is contraindicated during pregnancy; however, 1 dose of the vaccine is recommended after pregnancy (before discharge from the healthcare facility) in individuals with no evidence of immunity to rubella.¹⁰⁰

Individuals with HIV infection are at increased risk for severe complications if infected with measles.^{100 170 171 207} 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 and who do not have severe immunosuppression.^{100 108 124 207}

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^{† [off-label]} 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} 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 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}

During a measles outbreak (e.g., in child-care facilities, schools, colleges, hospitals), MMR vaccination is recommended in exposed individuals unless evidence of immunity can be provided.¹²⁴ During measles outbreaks, children as young as 6 months of age^{† [off-label]} 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} 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

Measles, Mumps, and Rubella Virus Vaccine Live Dosage and Administration

General

Dispensing and Administration Precautions

• Appropriate medical treatment used to manage immediate allergic reactions must be available in the event an acute anaphylactic reaction occurs following administration of MMR vaccine.¹⁹⁰

Administration

Administer by IM or sub-Q injection depending on the vaccine 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 age; consult the prescribing information for ProQuad for additional details.¹⁹⁴

MMR vaccines are supplied as single-dose vials of lyophilized antigen component; must reconstitute with accompanying sterile diluent (supplied in a vial or prefilled syringe) prior to administration.^{108 190} If diluent is supplied in a vial, withdraw entire volume of diluent from vial and inject into lyophilized vaccine vial.¹⁰⁸ If diluent is supplied as a prefilled syringe, transfer entire contents of prefilled syringe into vial containing lyophilized antigen.^{108 190}

A single dose of MMR vaccine after reconstitution is approximately 0.5 mL.^{108 190}

After reconstitution, withdraw and administer the entire volume immediately.^{108 190}

See manufacturer's prescribing information for additional details on preparation of individual vaccine preparations.^{108 190}

M-M-R II

Administer fixed-combination measles, mumps, and rubella vaccine labeled as M-M-R II by IM or sub-Q injection.¹⁰⁸

Priorix

Administer fixed-combination measles, mumps, and rubella vaccine labeled as Priorix by sub-Q injection only.¹⁹⁰

Dosage

Pediatric Patients

Prevention of Measles, Mumps, and Rubella Infection (Primary Immunization)

Infants and Children 12 Months through 6 Years of Age

IM or Sub-Q Depending on Specific Vaccine Preparation

For routine childhood immunization, administer first dose of MMR at 12–15 months of age and second dose at 4–6 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 first and second doses.^{102 108}

Alternatively, a 2-dose series with MMRV may be considered 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 MMR dose prior to their first birthday should receive additional doses of vaccine at 12–15 months of age and at 4–6 years of age to complete the vaccination series.¹⁰⁸

Children and Adolescents 7 through 18 Years of Age

IM or Sub-Q Depending on Specific Vaccine Preparation

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.^{99 100} The first and second doses should be administered at least 4 weeks apart. ^{102 124}

Alternatively, a 2-dose series with MMRV may be administered in children through 12 years of age; minimum interval between doses should be 3 months. ^{102 124}

Prevention of Measles, Mumps, and Rubella Infection (Postexposure Prophylaxis)

IM or Sub-Q Depending on Specific Vaccine Preparation

When used for postexposure prophylaxis of measles in individuals ≥12 months of age, 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^{† [off-label]}, who are considered too young to receive routine primary immunization, a single 0.5-mL dose of MMR should be given.¹²⁴

Outbreak Control

IM or Sub-Q Depending on Specific Vaccine Preparation

Additional 1 or 2 doses may be necessary during an outbreak situation depending on evidence of immunity.^{99 101 124}

When protection against measles is considered necessary for outbreak control in infants 6 through 11 months of age^{† [off-label]}, who are considered too young to receive routine primary immunization, a single 0.5-mL dose of MMR should be given.¹²⁴

Adults

Primary Immunization

IM or Sub-Q Depending on Specific Vaccine Preparation

For previously unvaccinated adults ≥19 years of age, administer 1 or 2 doses of MMR.^{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, administer 1 dose of MMR.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 no not have evidence of immunity to measles, mumps, or rubella, administer a 2-dose series with MMR if no previous doses of MMR were given; for those who previously received 1 dose of MMR, administer a second dose to complete the series.^{100 105} The minimum interval between doses is 4 weeks.^{100 105}

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

Postexposure Prophylaxis

IM or Sub-Q Depending on Specific Vaccine Preparation

When used for postexposure prophylaxis of measles, a single dose of MMR should be given within 72 hours of exposure.¹⁰⁸

Outbreak Control

IM or Sub-Q Depending on Specific Vaccine Preparation

Additional 1 or 2 doses may be necessary during an outbreak situation depending on evidence of immunity.^{99 101 124}

Special Populations

Hepatic Impairment

Manufacturers make no specific dosage recommendations.^{108 190}

Renal Impairment

Manufacturers make no specific dosage recommendations.^{108 190}

Geriatric Patients

Manufacturers make no specific dosage recommendations.^{108 190}

Cautions for Measles, Mumps, and Rubella Virus Vaccine Live

Contraindications

• Individuals with a history of hypersensitivity to any component of the MMR vaccine (including gelatin).^{108 190}

• Individuals with a history of anaphylaxis to neomycin.¹⁰⁸

• Individuals who are immunodeficient or immunosuppressed due to disease or medical therapy.^{108 190} Disseminated measles, mumps, and rubella virus infection have been reported in such individuals.^{108 190}

• Individuals with an active febrile illness with fever (>38.5°C).¹⁰⁸

• Individuals with active untreated tuberculosis.^{108 194}

• Individuals who are pregnant or who are planning on becoming pregnant within the next month.^{108 190}

Warnings/Precautions

Febrile Seizures

Febrile seizures have occurred rarely.^{108 109 114 144 170 190} Children with a personal or family history of seizures may be at increased risk.^{108 114 124 170}

Some evidence suggests higher rates of fever and febrile seizures 5 to 12 days after administration of 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 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, advise parents and guardians of children with a personal or family history of seizures of the risk of seizures after measles immunization.¹²⁴ Children receiving anticonvulsants should continue such therapy after vaccination.¹²⁴

Hypersensitivity

Allergic or immediate hypersensitivity reactions reported rarely.^{108 185 124} Do not administer to people who have had a severe allergic reaction to a previous dose of measles-containing vaccine or to a 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.¹⁰⁸ Consider potential benefits and risks carefully prior to administration of MMR to individuals with a history of immediate hypersensitivity reactions to egg ingestion.¹⁰⁸

Because MMR (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 AAP states that MMR may be used in individuals with a non-anaphylactic neomycin allergy.¹²⁴

Some preparations of MMR (e.g., tip caps of prefilled syringes of diluent supplied with Priorix) contain natural rubber latex, which may cause allergic reactions.¹⁹⁰

Thrombocytopenia

Measles virus-containing vaccines (e.g., MMR) rarely can cause clinically evident thrombocytopenia (e.g., purpura) within 2 months after vaccination; risk is higher after first dose than after second dose.^{108 124 170 175 176 177 178 179 181 182 190}

Carefully evaluate 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

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

Immune Globulins and Transfusions

Do not administer immune globulin and other blood products 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

Syncope

Syncope can occur in association with administration of injectable vaccines, including MMR.¹⁹⁰

Risk of Virus Transmission

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 reported.¹⁹⁰

Limitation of Vaccine Effectiveness

Vaccination with MMR may not protect all susceptible individuals from measles, mumps, or rubella infection.¹⁹⁰

Specific Populations

Pregnancy

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}

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

Lactation

Not known whether measles, mumps, or varicella vaccine virus is secreted in human milk.^{108 190}

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

ACIP states that it is safe for breastfeeding women to receive MMR vaccination.⁹⁹

Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for these vaccines, and any potential adverse effects on the breastfed child from the vaccine or underlying maternal condition.^{108 190} For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.^{108 190}

Pediatric Use

MMR not approved for use in individuals <12 months of age; however, has been used for postexposure prophylaxis and outbreak control in infants as young as 6 months of age^{† [off-label]}.^{99 124 190}

Safety and efficacy of MMR in infants <6 months of age not established.^{108 190}

Geriatric Use

Clinical studies of MMR did not include sufficient numbers of individuals ≥65 years of age to determine whether these individuals respond differently than younger individuals. ¹⁰⁸

Common Adverse Effects

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 receiving Priorix: local reactions including pain and redness.¹⁹⁰

Drug Interactions

Corticosteroids and Immununosuppressive Drugs

Individuals receiving immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticotropin, corticosteroids [at immunosuppressive dosages], radiation therapy) may have diminished response to MMR and replication of the virus may be potentiated.¹⁰⁸

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 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 Product

Antibodies contained in immune globulin preparations may interfere with the immune response to certain live virus vaccines, including measles virus-containing vaccines.^{108 124 170}

Blood products (e.g., whole blood, packed RBCs, plasma) also may interfere with the immune response to certain live virus vaccines, including MMR.¹²⁴

Specific recommendations for intervals between administration of immune globulin or blood products and live virus vaccines are provided in expert guidelines.¹²⁴

Tuberculin Skin Testing

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

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

Vaccines

Both 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}

Stability

Storage

Parenteral

M-M-R II

Store lyophilized antigen component at -50 to 8°C.¹⁰⁸ Prior to reconstitution, store at 2–8°C.¹⁰⁸

Store diluent in 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 reconstituted vaccine at 2–8°C for up to 8 hours; protect from light.¹⁰⁸

Priorix

Store lyophilized antigen component at 2–8°C; protect from light.¹⁹⁰ Store diluent in refrigerator (2–8°C) or at room temperature (up to 25°C).¹⁹⁰

Administer immediately after reconstitution.¹⁹⁰ If not administered immediately, may store reconstituted vaccine at 2–8°C for up to 8 hours; do not freeze.¹⁹⁰

Actions

• Fixed-combination preparation containing live attenuated measles, mumps, and rubella viruses.^{108 185 190}

• Stimulates active immunity to measles by inducing production of measles-specific IgG and IgM antibodies (humoral immunity) and also induces a cell-mediated immune response.^{108 196}

• Rubella vaccine component induces both humoral and cellular immunity.¹⁰⁵

• Mumps vaccine component produces a subclinical, noncommunicable infection probably involving both humoral and cellular immune response.¹⁰⁵

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling.¹⁰⁸

• Provide the required vaccine information to the patient, parent, or guardian.^{108 190}

• Inform the patient, parent, or guardian of the benefits and risks associated with vaccination.^{108 190}

• Question the patient, parent, or guardian about reactions to any previous doses of MMR vaccine.¹⁰⁸

• Inform the patient, parent, or guardian that vaccination with MMR vaccine may not offer 100% protection from measles, mumps, and rubella infection.¹⁰⁸

• Instruct patients, parents, or guardians to report any adverse reactions to their healthcare provider.¹⁰⁸

• Advise patients that the U.S. Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine.¹⁰⁸ For information or a copy of the vaccine reporting form, call the VAERS toll-free number at 1-800-822-7967, or report online at [Web].¹⁰⁸

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.^{108 190}

• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.^{108 190} Question females of reproductive potential regarding the possibility of pregnancy.^{108 190} Inform patients to avoid pregnancy for 1 month following vaccination.^{108 190}

• Inform patients of other important precautionary information.^{108 190}

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.

Preparations

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