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Measles, Mumps, and Rubella Virus Vaccine

Pronunciation

(MEE zels, mumpz & roo BEL a VYE rus vak SEEN)

Index Terms

  • Measles
  • MMR
  • Mumps
  • Mumps, Measles and Rubella Vaccines
  • Rubella
  • Rubella, Measles and Mumps Vaccines

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution [preservative free]:

M-M-R II: Measles virus ≥1000 TCID50, mumps virus ≥20,000 TCID50, and rubella virus ≥1000 TCID50 [contains albumin (human), bovine serum, chicken egg protein, gelatin, neomycin, sorbitol, and sucrose 1.9 mg/vial; supplied with diluent]

Brand Names: U.S.

  • M-M-R II

Pharmacologic Category

  • Vaccine
  • Vaccine, Live (Viral)

Pharmacology

As a live, attenuated vaccine, MMR vaccine offers active immunity to disease caused by the measles, mumps, and rubella viruses.

Onset of Action

The median seroconversion after 1 vaccine dose is 96% (measles), 99% (rubella), mumps (94%) (CDC/ACIP [McLean 2013]).

Duration of Action

The median duration of immunity after 2 doses is ≥15 years for all components of the vaccine (CDC/ACIP [McLean 2013]).

Use: Labeled Indications

Measles, mumps, and rubella prophylaxis: Active immunization for simultaneous vaccination against measles, mumps, and rubella in patients ≥12 months of age

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for the following (CDC/ACIP [McLean 2013]):

• All children (first dose given at 12 to 15 months of age)

• Adults born in 1957 or later (without evidence of immunity or documentation of vaccination). Vaccine may be given to adults born prior to 1957 if they do not have contraindications to the MMR vaccine.

• Adults at higher risk for exposure to and transmission of measles mumps and rubella should receive special consideration for vaccination, unless an acceptable evidence of immunity exists. This includes international travelers, persons attending colleges and other post high school education, persons working in healthcare facilities.

Contraindications

Hypersensitivity to measles, mumps, and/or rubella vaccine or any component of the formulation (including neomycin); current febrile respiratory illness or other febrile infection; patients receiving immunosuppressive therapy (does not include corticosteroids as replacement therapy); primary and acquired immunodeficiency states; individuals with blood dyscrasias, leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic systems; family history of congenital or hereditary immunodeficiency (until immune competence in the vaccine recipient is demonstrated); pregnancy

Dosing: Adult

Note: The minimum interval between 2 doses of MMR vaccine is 28 days (CDC/ACIP [McLean 2013]).

Immunization: SubQ: 0.5 mL per dose; 1 or 2 doses administered at least 28 days apart based upon the following criteria (CDC/ACIP [McLean 2013]):

Adults born in or after 1957 should be vaccinated unless they have acceptable evidence of immunity.

Adults born prior to 1957 are considered immune to measles, mumps, and rubella but may be vaccinated if they do not have contraindications to the vaccine. Pregnant adults born prior to 1957 are not considered immune to rubella.

Healthcare personnel: Persons born in or after 1957 should have 2 doses of vaccine unless they have acceptable evidence of immunity. Unvaccinated persons born prior to 1957 should also consider vaccination with 2 doses unless they have laboratory evidence or laboratory confirmation of disease.

HIV infection (without severe immunosuppression): Two doses of MMR unless there is acceptable evidence of immunity.

Household/close contacts of immunocompromised persons: Two doses of MMR unless there is acceptable evidence of immunity.

International travelers: Two doses of MMR prior to travel unless there is acceptable evidence of immunity.

Measles, mumps, or rubella outbreak (community): Adults who received 1 dose of MMR should be considered for a second dose if the outbreak involves measles or mumps in adults. Vaccination should also be considered for persons born prior to 1957 without evidence of immunity who may be exposed to mumps. A single dose of a rubella-containing vaccine is considered adequate vaccination during a rubella outbreak.

Measles, mumps, or rubella outbreak (healthcare facility): Unvaccinated health care personnel without evidence of immunity regardless of birth year should receive 2 doses during a measles or mumps outbreak and one dose during a rubella outbreak.

Students: Persons entering post high school educational facilities should receive 2 doses of MMR unless they have acceptable evidence of immunity prior to enrollment.

Women of childbearing potential: One dose of MMR unless they have acceptable evidence of immunity. Vaccination should not be given during pregnancy and pregnancy should be avoided for 28 days after vaccine administration.

Dosing: Pediatric

Note: The minimum interval between 2 doses of MMR vaccine is 28 days (CDC/ACIP [McLean 2013]).

Primary immunization: Children ≥12 months: SubQ: 0.5 mL per dose. One dose is recommended at 12 to 15 months of age and repeated at 4 to 6 years of age; the second dose is recommended prior to entering kindergarten or first grade. The second dose may be administered at any time provided at least 28 days have elapsed since the first dose (CDC/ACIP [McLean 2013]).

HIV infection without evidence of MMR immunity: Children ≥12 months: SubQ: 0.5 mL per dose. Children with HIV infection and without evidence of severe immunosuppression should have 2 doses of MMR. Those with perinatal HIV infection who were vaccinated prior to effective ART should have 2 additional doses of MMR once ART is established (CDC/ACIP [McLean 2013]).

Household/close contacts of immunocompromised persons: Children ≥12 months: SubQ: 0.5 mL per dose; 2 doses of MMR administered at least 28 days apart unless they have acceptable evidence of immunity (CDC/ACIP [McLean 2013]).

International travel:

Infants 6 to 11 months: SubQ: 0.5 mL per dose. Infants without evidence of immunity traveling internationally should receive 1 dose of MMR before departure from the United States; these infants should be revaccinated with 2 doses of MMR with the first dose between 12 to 15 months of age (and at least 28 days after the previous dose; target 12 months of age if child remains in area where disease risk is high) and the second dose at least 28 days later (ACIP [Robinson 2016]; CDC/ACIP [McLean 2013]).

Children ≥12 months and Adolescents: SubQ: 0.5 mL per dose. Children without evidence of immunity traveling internationally should receive 2 doses of MMR before departure from the United States. The second dose administered at least 28 days later (CDC/ACIP [McLean 2013]).

Measles outbreak:

Infants 6 to 11 months: SubQ: 0.5 mL per dose. If there is risk of exposure to measles involving infants, 1 dose of MMR vaccine may be administered (CDC/ACIP [McLean 2013]).

Children ages 1 to 4 years: SubQ: 0.5 mL per dose. Children who received one dose of MMR should be considered for a second dose if the outbreak involves preschool-aged children (CDC/ACIP [McLean 2013]).

Mumps outbreak: Children ages 1 to 4 years: SubQ: 0.5 mL per dose. Children who received 1 dose of MMR should be considered for a second dose if the outbreak involves preschool-aged children (CDC/ACIP [McLean 2013]).

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling.

Reconstitution

Use entire contents of the provided diluent to reconstitute vaccine. Gently agitate to mix thoroughly. Discard if powder does not dissolve. Use as soon as possible following reconstitution (may be stored at 2°C to 8°C (36°F to 46°F); protect from light); discard if not used within 8 hours.

Administration

Administer SubQ in outer aspect of the upper arm in patients ≥12 months. Not for IV administration. The minimum interval between 2 doses of MMR vaccine is 28 days (CDC/ACIP [McLean 2013]). Priorix (Canadian product, not available in the US) may also be given by IM injection. To prevent syncope related injuries, adolescents and adults should be vaccinated while seated or lying down (NCIRD/ACIP 2011). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.

Compatibility

Do not mix with other vaccines or injections. Separate needles and syringes should be used for each injection.

Storage

To maintain potency, the lyophilized vaccine must be stored between -50°C to 8˚C (-58°F to 46˚F). Temperatures below -50°C (-58°F) may occur if stored in dry ice. Prior to reconstitution, store the powder at 2°C to 8°C (36°F to 46°F). Protect from light. Diluent may be stored in refrigerator or at room temperature. Do not freeze diluent. Use as soon as possible following reconstitution, may be stored under refrigeration for up to 8 hours.

Drug Interactions

AzaTHIOprine: May enhance the adverse/toxic effect of Vaccines (Live). AzaTHIOprine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose azathioprine (3 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of azathioprine should be avoided. Consider therapy modification

Belimumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification

Daclizumab: May enhance the adverse/toxic effect of Vaccines (Live). Daclizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Dimethyl Fumarate: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Canadian labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. U.S. labeling does not mention this. Consider therapy modification

Fingolimod: May enhance the adverse/toxic effect of Vaccines (Live). Vaccinal infections may develop. Fingolimod may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Immune Globulins: May diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Consider therapy modification

Immunosuppressants: May enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: AzaTHIOprine; Beclomethasone (Oral Inhalation); Betamethasone (Systemic); Budesonide (Systemic); Corticotropin; Cortisone; Cytarabine (Liposomal); Deflazacort; Dexamethasone (Systemic); Fludrocortisone; Fluticasone (Oral Inhalation); Hydrocortisone (Systemic); Leflunomide; Mercaptopurine; Methotrexate; MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE; Triamcinolone (Systemic). Avoid combination

Leflunomide: May enhance the adverse/toxic effect of Vaccines (Live). Leflunomide may diminish the therapeutic effect of Vaccines (Live). Management: The ACIP guidelines state that live-attenuated vaccines should generally be avoided for at least 3 months after cessation of immunosuppressant therapy. However, the ACR does not recommend avoiding live vaccines in patients being treated with leflunomide. Consider therapy modification

Mercaptopurine: May enhance the adverse/toxic effect of Vaccines (Live). Mercaptopurine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose 6-mercaptopurine (1.5 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of mercaptopurine should be avoided. Consider therapy modification

Methotrexate: May enhance the adverse/toxic effect of Vaccines (Live). Methotrexate may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose methotrexate (0.4 mg/kg/week or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of methotrexate should be avoided. Consider therapy modification

Tuberculin Tests: Vaccines (Live) may diminish the diagnostic effect of Tuberculin Tests. Management: If a parenteral live vaccine has been recently administered, a scheduled PPD skin test should not be administered for at least 4-6 weeks following the administration of the vaccine. Consider therapy modification

Venetoclax: May enhance the adverse/toxic effect of Vaccines (Live). Venetoclax may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live, attenuated vaccines before, during, or after (prior to B-cell recovery) venetoclax treatment. Avoid combination

Test Interactions

Temporary suppression of tuberculin skin test reactivity. Tuberculin test may be given prior to vaccination, simultaneously at separate sites on the same day as measles-containing vaccine, or 4 to 6 weeks later (CDC/ACIP [McLean 2013]).

Adverse Reactions

All serious adverse reactions must be reported to the US Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS) 1-800-822-7967 or online at https://vaers.hhs.gov/esub/index. In Canada, adverse reactions may be reported to local provincial/territorial health agencies or to the Vaccine Safety Section at Public Health Agency of Canada (1-866-844-0018).

Frequency not always defined:

Cardiovascular: Syncope, vasculitis

Central nervous system: Acute disseminated encephalomyelitis, ataxia, dizziness, Guillain-Barré syndrome, headache, irritability, malaise, nerve deafness, paresthesia, polyneuropathy, retrobulbar neuritis, seizure, subacute sclerosing panencephalitis, transverse myelitis

Dermatologic: Erythema multiforme, morbilliform rash, pruritus, rash, Stevens-Johnson syndrome, urticaria

Endocrine & metabolic: Diabetes mellitus

Gastrointestinal: Diarrhea, nausea, pancreatitis, parotitis, sore throat, vomiting

Genitourinary: Epididymitis, orchitis

Hematologic & oncologic: Leukocytosis, lymphadenopathy (regional), purpura, thrombocytopenia

Hypersensitivity: Anaphylactoid reaction, anaphylaxis, angioedema

Infection: Atypical measles

Local: Injection site reaction (including burning, induration, redness, stinging, swelling, tenderness, vesiculation, wheal and flare)

Neuromuscular & skeletal: Arthropathy (arthralgia/arthritis: Women 12% to 26%; children ≤3%), myalgia, panniculitis

Ophthalmic: Conjunctivitis, oculomotor nerve paralysis, optic neuritis, optic papillitis, retinitis

Otic: Otitis media

Respiratory: Bronchospasm, cough, pneumonia, pneumonitis, rhinitis

Miscellaneous: Febrile seizures, fever

<1% (Limited to important or life-threatening): Aseptic meningitis (associated with Urabe strain of mumps vaccine), brain disease, encephalitis

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (NCIRD/ACIP 2011).

• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (NCIRD/ACIP 2011).

Disease-related concerns:

• Acute illness: May consider deferring administration in patients with moderate or severe acute illness (with or without fever). Although fever is a contraindication per the manufacturer, current guidelines allow for administration to patients with mild acute illness (without fever) (CDC/ACIP [McLean 2013]; NCIRD/ACIP 2011).

• CNS disorders: Use with caution in patients with history of cerebral injury, seizures, or other conditions where stress due to fever should be avoided.

• Measles exposure: Exposure to measles is not a contraindication to vaccine; use within 72 hours of exposure may provide some protection.

• Mumps exposure: Postexposure vaccination has not been shown to prevent or alter disease following mumps exposure (CDC/ACIP [McLean 2013]).

• Rubella exposure: Postexposure vaccination has not been shown to prevent or alter disease following rubella exposure (CDC/ACIP [McLean 2013]).

• Thrombocytopenia: Use with caution in patients with thrombocytopenia and those who develop thrombocytopenia after first dose; thrombocytopenia may worsen.

• Tuberculosis: Defer vaccination in patients with active untreated tuberculosis.

Concurrent drug therapy issues:

• Immune globulins: Recent administration of immune globulins may interfere with immune response.

• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The use of combination vaccines is generally preferred over separate injections, taking into consideration provider assessment, patient preference, and potential adverse events. When using combination vaccines, the minimum age for administration is the oldest minimum age for any individual component; the minimum interval between dosing is the greatest minimum interval between any individual components. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible (NCIRD/ACIP 2011).

Special populations:

• Altered immunocompetence: Use is contraindicated in severely immunocompromised patients. The ACIP does not recommend vaccination for persons with primary or acquired immunodeficiency (including immunosuppression associated with cellular immunodeficiency, hypogammaglobulinemia, dysgammaglobulinemia and AIDs, or severe immunosuppression associated with HIV); persons with blood dyscrasia, leukemia, lymphoma, or other malignant neoplasms which affect the bone marrow or lymphatic system; persons with a family history of congenital or hereditary immunodeficiency in first degree relatives (unless immunocompetence can be established); persons taking systemic corticosteroid therapy for ≥2 weeks in doses of corticosteroids ≥2 mg/kg of body weight or prednisone (or equivalent) ≥20 mg/day for persons who weigh >10 kg. Patients with HIV infection, who are asymptomatic and not severely immunosuppressed may be vaccinated (severe immunosuppression is defined as CD4+ T-lymphocyte <15% at any age or CD4 count <200 lymphocytes/mm3 for persons >5 years) (CDC/ACIP [McLean 2013]). Patients with leukemia who are in remission and who have not received chemotherapy for at least 3 months may be vaccinated. In general, household and close contacts of persons with altered immunocompetence may receive all age appropriate vaccines (NCIRD/ACIP 2011).

• Healthcare workers: Acceptable evidence of immunity is recommended for healthcare workers (CDC/ACIP [McLean 2013]).

• Pediatric: Safety and efficacy of measles vaccine has not been established in children <6 months of age and safety and efficacy of mumps and rubella vaccines have not been established in <12 months of age. Local health departments may recommend vaccine to children 6 to 12 months of age in outbreak situations, but this would not count towards their immunization series.

• Students: Acceptable evidence of immunity is recommended for students entering post high school educational institutions (CDC/ACIP [McLean 2013]).

• Travelers to endemic areas: Acceptable evidence of immunity is recommended for travelers to endemic areas.

Dosage form specific issues:

• Egg allergy: Vaccine may contain trace amounts of chick embryo antigen. Use caution in patients with history of immediate hypersensitivity/anaphylactic reactions following egg ingestion. Generally, the MMR vaccine can be safely administered to persons with an egg allergy (NCIRD/ACIP 2011).

• Gelatin: Products may contain gelatin. Use is contraindicated in patients with a history of anaphylactic/anaphylactoid reaction to gelatin

• Neomycin sensitivity: Manufactured with neomycin. Use is contraindicated in patients with history of anaphylactic/anaphylactoid reactions to neomycin. Contact dermatitis due to neomycin is not a contraindication to the vaccine.

Other warnings/precautions:

• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (NCIRD/ACIP 2011). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula 2009).

• Appropriate use: Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the ACIP Recommended Adult Immunization Schedule (ACIP [Kim 2016]). Specific recommendations for vaccination in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions as well as contacts of immunocompromised patients are available from the IDSA (Rubin 2014).

• Blood products: Recent administration of blood or blood products may interfere with immune response.

• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (NCIRD/ACIP 2011).

Monitoring Parameters

Monitor for syncope for 15 minutes following administration (NCIRD/ACIP 2011). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. It is not known whether this vaccine can cause fetal harm or affect reproduction capacity. Based on information collected following inadvertent administration during pregnancy, adverse events have not been observed following use of rubella vaccine. However, theoretical risks cannot be ruled out; use of this vaccine is contraindicated in pregnant females and should not be administered to women trying to conceive. The manufacturer recommends that pregnancy be avoided for 3 months after vaccine administration. The Advisory Committee on Immunization Practices (ACIP) recommends that pregnancy should be avoided for 28 days following vaccination. The risk of congenital rubella syndrome following vaccination is significantly less than the risk associated following infection; therefore, inadvertent administration of MMR during pregnancy is not considered an indication to terminate pregnancy.

Adverse consequences of natural infection in unvaccinated pregnant women have been reported. Measles infection during pregnancy may increase the risk of premature labor, preterm delivery, spontaneous abortion and low birth weights. Rubella infection during the first trimester may lead to miscarriages, stillbirths, and congenital rubella syndrome (includes auditory, ophthalmic, cardiac and neurologic defects; intrauterine and postnatal growth retardation); fetal rubella infection can occur during any trimester of pregnancy. Maternal mumps infection during the first trimester may increase the risk of spontaneous abortion or intrauterine fetal death. Sterility in males and infertility in prepubescent females may also occur with natural mumps infection.

Prenatal screening is recommended for all pregnant women who lack evidence of rubella immunity. Women of childbearing age without documentation of rubella vaccination or serologic evidence of immunity should be vaccinated (for women of childbearing potential, birth prior to 1957 is not acceptable evidence of immunity to rubella). Women who are pregnant should be vaccinated upon completion or termination of pregnancy, prior to discharge. Household contacts of pregnant women may be vaccinated (CDC/ACIP [McLean, 2013]).

Patient Education

• Discuss specific use of vaccine and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience burning, stinging, joint pain, or joint edema. Have patient report immediately to prescriber behavioral changes, severe dizziness, passing out, seizures, severe headache, testicular edema, bruising, bleeding, or abnormal gait (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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