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Measles, Mumps, and Rubella Vaccine

Class: Vaccines
ATC Class: J07BJ01
VA Class: IM100
Brands: M-M-R II, ProQuad

Introduction

Live, attenuated virus vaccine.1 11 Measles, mumps, and rubella virus vaccine live (MMR) is a fixed-combination vaccine containing measles, mumps, and rubella antigens and is used to stimulate active immunity to measles, mumps, and rubella.1 MMR also commercially available in the US as a fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad).66

Uses for Measles, Mumps, and Rubella Vaccine

Prevention of Measles, Mumps, and Rubella

Prevention of measles, mumps, and rubella in adults, adolescents, and children ≥12 months of age.1 5 8 10 14 43 44 50

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and American Academy of Family Physicians (AAFP) recommend that all children be vaccinated against measles, mumps, and rubella using a 2-dose regimen of MMR beginning at 12 through 15 months of age, unless contraindicated.5 8 14 43 44 (See Contraindications under Cautions.) In addition, catch-up vaccination with MMR is recommended for all children and adolescents up to 18 years of age who are unvaccinated or have previously received only a single dose.5 8 43 44

ACIP, AAP, AAFP, American College of Obstetricians and Gynecologists (ACOG), and American College of Physicians (ACP) recommend that all adults receive 1 or 2 doses of MMR, unless they have evidence of immunity to measles, mumps, and rubella.14 44 50

The fixed-combination vaccine containing MMR and varicella vaccine (MMRV; ProQuad) may be used in children 12 months through 12 years of age when a dose of MMR and a dose of varicella vaccine is indicated.27 65 66 72 Although use of MMRV (ProQuad) reduces the number of required injections when both vaccines are indicated during a single health-care visit, there is some evidence that the relative risk for fever and febrile seizures in infants 12 through 23 months of age may be higher with MMRV (ProQuad) than when a dose of MMR and a dose of Varivax are given concomitantly at separate sites.65 66 72 (See Use of Fixed Combinations under Cautions.)

Although monovalent vaccines containing measles, mumps, or rubella antigens have been used to stimulate active immunity to measles, mumps, or rubella,2 3 4 8 11 14 43 44 50 these single-antigen vaccines are no longer commercially available in the US.70 MMR vaccine should be used to complete immunization against measles, mumps, and rubella in adults, adolescents, or children who previously received single doses of the monovalent vaccines.70

CDC states that individuals already immune to measles, mumps, or rubella because of previous vaccination or natural disease can receive MMR without an increased risk of adverse reactions.70

Evidence of measles immunity. Individuals born before 1957 generally are considered immune to measles.8 44 50 71 Individuals born during or after 1957 can be considered immune to measles if there is documentation of adequate immunization against measles (2 doses of MMR or measles-containing vaccine with first dose given on or after 12 months of age and second dose given at least 28 days after first dose), natural measles infection diagnosed by a health-care provider, laboratory evidence of measles immunity, or laboratory confirmation of measles infection.8 44 50 71 All individuals without evidence of immunity should be considered susceptible to measles and should receive 2 doses of MMR, unless contraindicated.8 44 50 In addition, individuals vaccinated against measles prior to 1968 received measles vaccine that is less immunogenic than the currently available vaccine and should be revaccinated with MMR.44 50

Evidence of mumps immunity. Individuals born before 1957 generally are considered immune to mumps.8 10 44 50 71 Individuals born during or after 1957 can be considered immune to mumps if there is documentation of adequate vaccination against mumps (2 doses of MMR or mumps-containing vaccine for school aged-children in grades K-12, college students, health-care personnel, international travelers; at least 1 dose in adults not at high risk), natural mumps infection diagnosed by a health-care provider, laboratory evidence of mumps immunity, or laboratory confirmation of mumps infection.10 44 50 71 All individuals without evidence of immunity should be considered susceptible to mumps and should be vaccinated, unless contraindicated.8 10 44 50

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Evidence of rubella immunity. Individuals who have documentation of adequate vaccination (at least 1 dose of MMR or rubella-containing vaccine given at ≥12 months of age) or serologic evidence of rubella immunity are considered immune to rubella.8 14 44 50 71 Birth before 1957 only provides presumptive evidence of rubella immunity and does not guarantee immunity.14 71 Clinical diagnosis of rubella is unreliable and should not be considered when assessing immune status.8 14 44 All women of childbearing age, regardless of birth year, should be tested for rubella immunity and counseled regarding congenital rubella syndrome (CRS).8 44 Nonpregnant women without evidence of immunity should be vaccinated; those who are pregnant should be vaccinated during the immediate postpartum period.3 8 44 50 54 (See Pregnancy under Cautions.)

Health-care personnel should be immune to measles, mumps, and rubella.10 44 46 Those without evidence of immunity to measles and mumps (2 doses of measles virus-containing and mumps virus-containing vaccine with first dose given on or after 12 months of age and second dose given at least 28 days after first dose, laboratory evidence of immunity, laboratory confirmation of disease) and those without evidence of immunity to rubella (at least 1 dose of a rubella virus-containing vaccine on or after 12 months of age, laboratory evidence of immunity, laboratory confirmation of disease) should receive 2 doses of MMR.10 44 46 71 Health-care personnel who have received only a single dose should receive a second dose.10 44 46 71 Because birth before 1957 is only presumptive evidence of immunity, health-care facilities should consider recommending 2 doses of MMR during an outbreak of measles or mumps for unvaccinated personnel born before 1957 who do not have laboratory evidence of immunity to measles and mumps or laboratory confirmation of these diseases and should consider recommending 1 dose of MMR for individuals in this age group during an outbreak of rubella.10 44 46 71

Travelers may be at high risk of exposure to measles, mumps, and rubella outside the US and should be immune to these diseases before leaving the US.8 9 14 44 52 Measles occurs worldwide and remains endemic in many countries;8 9 44 many measles cases reported in the US occur from exposure to the disease in foreign countries.8 9 44 73 Mumps remains endemic in many countries9 and rubella occurs worldwide9 and is endemic and may be epidemic in many countries.14

HIV-infected individuals are at increased risk for severe complications if infected with measles.8 31 32 44 76 ACIP, AAP, CDC, National Institutes of Health (NIH), IDSA, Pediatric Infectious Diseases Society, and others state that all asymptomatic HIV-infected children, adolescents, and adults should receive MMR according to the usually recommended immunization schedules.8 11 14 15 31 32 44 75 76 In addition, MMR should be considered for all symptomatic HIV-infected individuals who do not have evidence of severe immunosuppression and who otherwise would be eligible for vaccination.8 11 14 15 31 32 44 75 76 MMR is contraindicated in HIV-infected individuals who are severely immunosuppressed (i.e., children <12 months of age with CD4+ T-cell count <750/mm3; children 1 through 5 years of age with CD4+ T-cell count <500/mm3; children ≥6 years of age, adolescents, and adults with CD4+ T-cell count <200/mm3; children <13 years of age with CD4+ T-cell percentage <15%);1 8 15 31 32 44 75 75 76 such individuals should receive immune globulin IM (IGIM) if protection against measles is needed (e.g., in travelers, following exposure to measles).8 15 31 32 44 75 AAP and ACIP recommend that HIV-infected individuals receive IGIM following exposure to measles, regardless of their vaccination status.8 15 31 44

Internationally adopted children whose immune status is uncertain should either be revaccinated or have serologic tests performed to confirm immunity to measles, mumps, and rubella.9 11 The child may have received monovalent measles vaccine in their country of origin, but MMR is not used in most countries.9 Therefore, although serologic testing is available to verify immunization status in children ≥12 months of age,9 11 CDC states that administration of MMR is preferable to serologic testing unless there is documentation that the child has had mumps and rubella.9 ACIP states that the simplest approach is to revaccinate with 1 or 2 doses of MMR according to the US recommended childhood and adolescent immunization schedule.11 (See Dosage and Administration.)

Postexposure Vaccination and Outbreak Control of Measles

Postexposure vaccination (given within 72 hours of exposure) with MMR may provide some protection against measles and provides future protection in individuals who do not contract the disease.1 8 9 44 50 52

For most situations (including measles outbreaks in schools or childcare centers), postexposure vaccination within 72 hours of measles exposure is preferable to use of IGIM.8 44 If vaccine is contraindicated (e.g., infants <6 months of age, pregnant women, immunocompromised individuals) or it has been >72 hours but <6 days since exposure, susceptible individuals may receive an immediate dose of IGIM.8 9 44

If a measles outbreak occurs in a child-care facility, school (elementary, middle, junior high, senior high), college, university, or other secondary educational institution, ACIP and AAP recommend that all students (and their siblings) and all school personnel born during or after 1957 be vaccinated against measles, unless they have documentation indicating receipt of 2 doses of measles vaccine at ≥12 months of age or other evidence of measles immunity.8

During measles outbreaks, children as young as 6 months of age should be vaccinated if exposure to natural measles is considered likely.8 44 However, these children should be considered inadequately immunized and should receive the usual 2-dose MMR vaccination regimen beginning at 12 through 15 months of age.8 44 (See Infants 6 through 11 Months of Age (MMR) under Dosage and Administration.)

Postexposure Vaccination and Outbreak Control of Mumps

There is no evidence that postexposure vaccination provides protection against mumps; however, if exposure does not result in infection,4 8 44 52 postexposure vaccination may be given to provide protection against subsequent infection.8 44 52

Because about 90% of adults who have no knowledge of past infection are immune by serologic testing, postexposure vaccination with mumps virus vaccine live is not routinely indicated for individuals born prior to 1957 unless they are known to be seronegative;8 however, vaccination of such individuals also is not precluded and can be undertaken in outbreak settings.44

In an outbreak setting, ACIP recommends that consideration be given to administering a second dose of MMR or mumps vaccine to children 1–4 years of age and to adults at low risk (provided it has been at least 28 days since they received the first dose).10 44 In addition, in an outbreak setting, ACIP states that health-care facilities should strongly consider recommending 2 doses of MMR to unvaccinated personnel born before 1957 who do not have evidence of immunity.10 44

Postexposure Vaccination and Outbreak Control of Rubella

Postexposure vaccination with rubella vaccine has not been shown to prevent illness.3 8 14 Because postexposure vaccination provides future protection to individuals who do not contract the disease and because there is no evidence that administering the vaccine to an individual who is incubating rubella would be harmful, such vaccination is recommended by the ACIP and AAP, unless contraindicated.8 14 44

Rubella outbreak control is essential for eliminating indigenous rubella and preventing congenital rubella infection and CRS.14 54 Because the incidence of rubella is low in the US, CDC states that even a single case of rubella should be considered a potential outbreak.54 Report suspected cases of rubella, CRS, or congenital rubella infection to local health departments within 24 hours; do not delay reporting while waiting for laboratory confirmation.14 54 Implement control measures as soon as a case of rubella is identified; maintaining control measures is essential when pregnant women are possible contacts of patients with rubella.54

During a rubella outbreak, patients should be isolated for 5–7 days after rash onset and susceptible contacts identified and vaccinated (unless contraindicated).54 Pregnant women exposed to rubella who do not have adequate proof of immunity should be tested for serologic evidence of the disease.54 Susceptible pregnant women should be counseled regarding the risks for intrauterine rubella infection and should be advised to avoid activities where they might be exposed to rubella and to avoid contact with individuals with confirmed, probable, or suspected rubella for at least 6 weeks after rash onset in the last identified patient.54

If a rubella outbreak occurs in a congregate environment (e.g., household, jail, day-care center, military setting, school, place of worship, athletic event, other social gathering), exposed individuals without adequate proof of rubella immunity should be vaccinated.54 If an outbreak occurs in a health-care setting (e.g., hospital, doctor’s office, clinic, nursing home, other facility where patients receive subacute or extended care), health-care workers without adequate evidence of immunity should be excluded from work and vaccinated (especially in settings where pregnant women could be exposed).54 Despite subsequent vaccination, exposed health-care workers should be excluded from direct patient care for 23 days after the last exposure to rubella.54 Health-care facilities should strongly recommend a dose of a rubella-containing vaccine to workers born before 1957 who do not have serologic evidence of immunity.54 If a community-wide outbreak occurs, any person exposed to a patient with rubella or CRS who cannot demonstrate proof of immunity should be vaccinated or restricted from contact with patients with rubella or CRS.54

Consult CDC’s recommendations for evaluation and management of suspected rubella outbreaks for additional information, including information on criteria for rubella case classification (suspected, probable, confirmed, asymptomatic confirmed), criteria for case classification of CRS (suspected, probable, confirmed, infection only), laboratory diagnosis of rubella and CRS, surveillance and control measures, and outreach activities to prevent future rubella outbreaks.54

Measles, Mumps, and Rubella Vaccine Dosage and Administration

Administration

Sub-Q Administration

MMR (M-M-R II): Administer by sub-Q injection.1 11

MMRV (ProQuad): Administer by sub-Q injection.66

Do not administer IM or IV.1 66

Depending on patient age, administer sub-Q into the upper-outer triceps area or anterolateral thigh.1 11 66 For children ≥1 year of age, adolescents, and adults, the upper-outer triceps area usually is preferred.11

To ensure appropriate delivery, sub-Q injections should be made at a 45° angle using a 5/8-inch, 23- to 25-gauge needle.1 11

Prior to injection, ensure that needle is not in a blood vessel.1

Since syncope may occur following vaccination, observe vaccinees for approximately 15 minutes after the dose.11 Syncope occurs most frequently in adolescents and young adults.11 If syncope occurs, observe patient until symptoms resolve.11

May be given simultaneously with most other age-appropriate vaccines during the same health-care visit (using different syringes and different injection sites).1 5 8 11 14 44 47 50 66 (See Interactions.)

When multiple vaccines are administered during a single health-care visit, each vaccine should be given with a different syringe and at different injection sites.11 Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.11 If multiple vaccines must be given into a single limb, the deltoid may be used in older children and adults, but the anterolateral thigh is preferred in infants and younger children.11

Reconstitution

MMR (M-M-R II): Reconstitute lyophilized vaccine by adding entire amount of diluent supplied by the manufacturer to the corresponding vial of lyophilized vaccine and agitating the vial.1 Use only the diluent supplied by the manufacturer.1 Reconstituted vaccine occurs as a clear yellow solution.1

MMRV (ProQuad): Reconstitute lyophilized vaccine by adding entire amount of diluent provided by the manufacturer.66 Gently agitate vial.66 Use only the diluent supplied by the manufacturer.66 Reconstituted vaccine occurs as a clear pale yellow to light pink liquid.66

Use sterile syringes and needles free of preservatives, antiseptics, and detergents to avoid inactivating the live virus vaccine.1 66

To minimize loss of potency and ensure an adequate immunizing dose, administer immediately following reconstitution; discard reconstituted vaccine if not used within 8 hours.1 (See Stability.)

Dosage

MMR (M-M-R II): Used in adults, adolescents, and infants and children ≥6 months of age.1

MMRV (ProQuad): Used in children 12 months through 12 years of age.66

Pediatric Patients

Prevention of Measles
Infants 6 through 11 Months of Age (MMR)
Sub-Q

When protection against measles is considered necessary (e.g., for outbreak control, for children traveling to or residing in areas outside the US with an increased risk of measles) in children too young to have received routine primary measles immunization, give a single 0.5-mL dose of MMR.8 9 44 70

Such children should be considered inadequately immunized and should be revaccinated with the usual 2-dose MMR regimen initiated as soon as possible after their first birthday.8 9 44 (See Infants and Children 12 Months through 6 Years of Age (MMR) under Dosage and Administration.)

Prevention of Measles, Mumps, and Rubella
Infants and Children 12 Months through 6 Years of Age (MMR)
Sub-Q

Primary immunization consists of 2 doses.1 5 8 11 44 Each dose is 0.5 mL.1 8 11 44

ACIP, AAP, and AAFP recommend that first dose be given at 12 through 15 months of age and second dose be given at 4 through 6 years of age (just prior to entry into kindergarten or first grade).1 5 8 11 44 52 Second dose may be given earlier during any routine visit, provided at least 4 weeks (28 days) have elapsed since first dose and both first and second doses are administered at ≥12 months of age.5 8 11 44 52

Children and Adolescents 7–18 Years of Age (MMR)
Sub-Q

Primary immunization consists of 2 doses given at least 4 weeks apart.5 8 52 Each dose is 0.5 mL.1

Catch-up vaccination recommended at 11–12 years of age for unvaccinated or incompletely vaccinated individuals.8 43 44 52 All children and adolescents who previously received only a single dose should receive a second dose.8 44 52

Prevention of Measles, Mumps, Rubella, and Varicella
Infants and Children 12 Months Through 12 Years of Age (MMRV; ProQuad)
Sub-Q

Each dose is 0.5 mL.66

May be used when simultaneous administration of the first or second dose of MMR and first or second dose of varicella vaccine is indicated or whenever any component of the fixed-combination vaccine is indicated and the other components are not contraindicated.5 27 66

When considering use in infants and children 12 through 47 months of age, ACIP states that providers should advise the parent or caregiver about the benefits and risks associated with MMRV (ProQuad) compared with the individual component vaccines.72 (See Use of Fixed Combinations under Cautions.)

At least 1 month should elapse between a dose of a measles-containing vaccine (e.g., MMR) and a dose of MMRV (ProQuad) and preferably at least 3 months should elapse between a dose of varicella vaccine (Varivax ) and a dose of MMRV (ProQuad); however, if a second dose of a varicella-containing vaccine was administered at least 28 days following the first dose, the second dose does not need to be repeated.5 66

Adults

Prevention of Measles, Mumps, and Rubella
Adults ≥19 Years of Age (MMR)
Sub-Q

Primary immunization consists of 1 or 2 doses given at least 4 weeks (28 days) apart.1 8 11 44 52 Each dose is 0.5 mL.1 8 11 44

Special Populations

Hepatic Impairment

No specific dosage recommendations.1 66

Renal Impairment

No specific dosage recommendations.1 66

Cautions for Measles, Mumps, and Rubella Vaccine

Contraindications

  • MMR (M-M-R II) or MMRV (ProQuad)
  • Hypersensitivity to the vaccine or any component, including gelatin.1 66 (See Gelatin Allergy under Cautions.)

  • History of anaphylactic or anaphylactoid reaction to neomycin.1 66 (See Neomycin Allergy under Cautions.)

  • Blood dyscrasias, leukemia, lymphomas of any type, or any other malignant neoplasms affecting the bone marrow or lymphatic system.1 66 (See Individuals with Altered Immunocompetence under Cautions.)

  • Primary and acquired immunodeficiencies, including acquired immunodeficiency syndrome (AIDS) or other clinical manifestations of HIV infection, cellular immune deficiency, hypogammaglobulinemia, and dysgammaglobulinemia.1 66 (See Individuals with Altered Immunocompetence under Cautions.)

  • Immunosuppressive therapy (e.g., corticosteroids, antineoplastic agents, radiation).1 66 (See Specific Drugs and Laboratory Tests under Interactions.)

  • Family history of congenital or hereditary immunodeficiency, unless immune competence has been demonstrated in the potential vaccine recipient.1 66 (See Individuals with Altered Immunocompetence under Cautions.)

  • Febrile respiratory illness or other active febrile infection.1 66 (See Concomitant Illness under Cautions.)

  • Active untreated tuberculosis.1 66 (See Tuberculosis under Cautions.)

  • Pregnancy.1 66 (See Pregnancy under Cautions.)

Warnings/Precautions

Warnings

Individuals with Altered Immunocompetence

Because MMR and MMRV (ProQuad) contain live, attenuated viruses, they generally are contraindicated in individuals with altered immunocompetence, including those with primary or acquired immunodeficiencies or those receiving immunosuppressive therapy.1 8 11 50 66 (See Contraindications.)

Measles inclusion body encephalitis (MIBE), pneumonitis, and death related to disseminated measles vaccine virus infection have been reported in individuals with altered immunocompetence (e.g., AIDS) who received measles-containing vaccines.1 31 32 44

MMR is contraindicated in HIV-infected children, adolescents, and adults with evidence of severe immunosuppression (i.e., children <12 months of age with CD4+ T-cell count <750/mm3; children 1 through 5 years of age with CD4+ T-cell count <500/mm3; children ≥6 years of age, adolescents, and adults with CD4+ T-cell count <200/mm3; children <13 years of age with CD4+ T-cell percentage <15%).1 31 32 44 75 76 However, HIV-infected individuals are at increased risk for severe complications if infected with measles.11 31 32 44 76 Therefore, ACIP, AAP, NIH, IDSA, Pediatric Infectious Diseases Society, and others state that MMR can be used in HIV-infected children, adolescents, and adults who do not have evidence of severe immunosuppression.8 11 14 15 31 32 44 75 76 Do not use MMRV (ProQuad) in HIV-infected individuals;27 66 76 safety and efficacy of this fixed-combination vaccine not established in such individuals.66

ACIP states use of live virus vaccines can be considered in patients with leukemia, lymphoma, or other malignancies if the disease is in remission and chemotherapy was terminated at least 3 months prior to vaccination.11

Antibody responses to MMR and efficacy may be decreased in immunocompromised individuals.1 31 42 44

The presence of immunocompromised or HIV-infected individuals in a household does not preclude administration of MMR or MMRV (ProQuad) to other household members.8 14 27 44

CNS Effects

Encephalitis, encephalopathy, MIBE, subacute sclerosing panencephalitis (SSPE), Guillain-Barré syndrome (GBS), aseptic meningitis, seizures, ataxia, polyneuritis, polyneuropathy, ocular palsies, and paresthesia reported rarely.1 44

Adverse CNS reactions (encephalitis, encephalopathy) have been temporally associated with MMR, but causal relationship not established.1 44 Risk of serious neurologic disorders following measles vaccination is considerably less than the risk of encephalitis and encephalopathy associated with wild-type measles infection.1 8

Fever or Febrile Seizures

Fever (≥39.4°C) may occur; usually is evident 6–12 days after MMR and lasts 1–2 days.8 Febrile seizures have occurred rarely following administration of measles-containing vaccine.1 8 31 44

MMR: Use caution in individuals with a history of cerebral injury, individual or family history of seizures, or any other condition in which fever-induced stress should be avoided.1 8 Those receiving anticonvulsants should continue such therapy after vaccination.8 Monitor patient for temperature elevations following vaccination.1

MMRV (ProQuad): Use caution in individuals with a history of cerebral injury, individual or family history of seizures, or any other condition in which fever-induced stress should be avoided.66 (See Use of Fixed Combinations under Cautions.)

Interim results from an ongoing study indicate that the relative risk for febrile seizures 5–12 days after a dose of MMRV (ProQuad) in children 12–60 months of age (99% were 12–23 months of age) is 2.3 times higher than that reported with concurrent administration of a dose of Varivax and a dose of MMR given during a single health-care visit.65 (See Use of Fixed Combinations under Cautions.)

Thrombocytopenia

Thrombocytopenia reported after administration of MMR or monovalent vaccines containing measles, mumps, or rubella antigens (monovalent vaccines no longer commercially available in the US).1 8 37 38 39 40 44 Thrombocytopenia has worsened in those with preexisting thrombocytopenia and may worsen with subsequent doses.1 39

Consider potential benefits and risks when considering use of MMR in patients who developed thrombocytopenia or had worsening of thrombocytopenia with a previous dose.1 Serologic testing for antibody to measles, mumps, and rubella can be used to determine whether additional doses are necessary to provide protection.1

Risk of Transmissible Agents in Preparations Containing Albumin

MMR contains recombinant human albumin.1

MMRV (ProQuad) contains albumin human.66 Since albumin human is prepared from pooled human plasma, it is a potential vehicle for transmission of human viruses, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).66

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis, anaphylactoid reaction, bronchial spasm, rash, urticaria, angioedema (including peripheral or facial edema), erythema multiforme, and Stevens-Johnson syndrome reported rarely.1 31 44

Prior to vaccine administration, question recipient and/or parent or guardian concerning reactions to previous doses of the vaccine or similar preparations.1 66

Individuals who have a hypersensitivity reaction to the first dose should be tested for immunity to measles, mumps, and rubella; if results indicate immunity, a second dose is not necessary.8 Any individual with an anaphylactic reaction to a previous dose should not receive another dose, regardless of results of serologic testing.8

Epinephrine and other appropriate agents should be readily available in case anaphylaxis or similar reaction occurs.1 66

Gelatin Allergy

MMR and MMRV (ProQuad) contain hydrolyzed gelatin as a stabilizer,1 66 which may rarely result in hypersensitivity reactions in some individuals.31 34 35 44 Do not use in individuals with a history of anaphylactic reactions to gelatin or gelatin-containing products.1 11 31 44 66

Immediate reactions (i.e., wheezing and dyspnea with or without urticaria) and other reactions (i.e., erythema and swelling at injection site) have occurred and may be related to gelatin hypersensitivity.31 34

Although skin testing for gelatin sensitivity before administering a gelatin-containing vaccine can be considered, there are no specific protocols for this purpose.8 11 Because gelatin used in vaccines manufactured in the US usually is derived from porcine sources and food gelatin may be derived solely from bovine sources, a negative food history does not exclude the possibility of a reaction to the gelatin contained in the vaccine.8 44

Neomycin Allergy

MMR and MMRV (ProQuad) contain trace amounts of neomycin and are contraindicated in those with a history of anaphylactic reactions to neomycin.1 66

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.1 8 11 66 An erythematous pruritic nodule or papule may be evident 48–96 hours after vaccination.1

ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh risks.8 11

Manufacturer of MMRV (ProQuad) states that if use of this vaccine is considered medically necessary in an individual with a history of anaphylactic reactions to neomycin, an allergist or immunologist should be consulted and the vaccine should be given only in settings where anaphylactic reactions can be managed appropriately.66

Allergy to Egg-related Antigens

MMR and MMR component of MMRV (ProQuad) is produced in chick embryo cell culture.1 11 66

Individuals with a history of anaphylactic, anaphylactoid, or other immediate hypersensitivity reactions (e.g., hives, swelling of the mouth or throat, difficulty breathing, hypotension, shock) after egg ingestion may be at increased risk of immediate-type hypersensitivity reactions after receiving vaccines containing traces of chick embryo antigen.1 66

Consider potential benefits versus possible risks before administering MMR or MMRV (ProQuad) to an individual with a history of anaphylactic or other immediate hypersensitivity reaction to egg ingestion.1 66 Use extreme caution and have adequate treatment readily available in case a reaction occurs.1 66

Most individuals with a history of anaphylactic reactions to eggs are at low risk for anaphylactic reactions to MMR or MMRV (ProQuad);1 8 11 17 18 19 20 21 22 23 24 25 26 31 44 66 skin testing using the vaccines has not been predictive of which individuals will have reactions.1 8 66

Individuals who have egg allergies that are not anaphylactic in nature generally are not at increased risk of hypersensitivity reactions to vaccines produced in chick embryo cell cultures.1 8 11 66 There is no evidence that individuals with allergies to chickens or feathers are at increased risk of allergic reactions to such vaccines.1 8 66

General Precautions

Transmission of Vaccine Virus

MMR and MMRV (ProQuad) contain live, attenuated virus.1 66 There is a theoretical risk that transmission of vaccine virus could occur between vaccinees and susceptible contacts.1 66

Transmission of live, attenuated measles or mumps virus from vaccinees to susceptible contacts has not been reported.1

Although small amounts of the live, attenuated rubella virus are excreted from the nose or throat of most vaccinees 7–28 days after vaccination, there is no evidence that the vaccine virus is transmitted to susceptible contacts.1 14 52 However, rubella vaccine virus can be transmitted to infants via breast milk.1 (See Lactation under Cautions.)

Risk for transmission of live, attenuated varicella virus from individuals who receive MMRV (ProQuad) to susceptible close contacts is greatest if recipient develops a varicelliform rash following vaccination and/or the vaccine recipient is immunocompromised.27 Transmission of vaccine virus from vaccinees without a varicella-like rash has been reported, but not confirmed.66

Musculoskeletal Effects

Arthralgia and, rarely, transient arthritis may occur following vaccination with MMR or monovalent rubella vaccine (monovalent vaccine no longer commercially available in the US).3 14 44 52

Arthritis and arthralgia occur in up to 26% of susceptible adult women.3 14 44 Symptoms usually begin 1–4 weeks after vaccination and persist for 1 day to 3 weeks.14 Although these symptoms generally are well tolerated and rarely interfere with normal activities, they may persist for months or, rarely, for years.3 14 44 Joint symptoms are infrequent and generally of brief duration in children; the incidence in adolescent girls appears to be greater than that in children but less than that in adult women.3 14 44

Use of Fixed Combinations

When the fixed-combination vaccine containing measles, mumps, and rubella antigens (MMR) or the fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad) is used, consider contraindications and cautions related to each antigen.1 66

There is some evidence that the relative risk for febrile seizures in children 12–60 months of age after a dose of MMRV (ProQuad) is higher than that reported when a dose of MMR and a dose of monovalent varicella vaccine (Varivax) are given during a single health-care visit.65 (See Fever or Febrile Seizures under Cautions.)

When the first dose of MMR and first dose of varicella vaccine (Varivax) are indicated in infants and children 12 through 47 months of age, ACIP states that providers considering use of MMRV (ProQuad) should advise the parent or caregiver about the benefits and risks associated with MMRV (ProQuad) compared with the individual component vaccines.72 Although MMRV (ProQuad) results in 1 less injection, it is associated with a higher risk for fever and febrile seizures on days 5 through 12 after the first dose in children 12 through 23 months of age (i.e., 1 extra febrile seizure for every 2300–2600 doses of MMRV [ProQuad]).72 ACIP states that if providers face any barriers to clearly communicating these benefits and risks (e.g., language barrier), then MMR and monovalent varicella vaccine (Varivax) should be administered instead of MMRV (ProQuad).72

When the first dose of MMR and first dose of varicella vaccine (Varivax) are indicated in children ≥48 months of age and when second doses are indicated in those 15 months through 12 years of age, ACIP states that use of MMRV (ProQuad) generally is preferred over separate injections of the component vaccines;72 considerations should include provider assessment (e.g., number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient return, storage and cost considerations), patient preference, and potential for adverse effects.72

The manufacturer recommends that MMRV (ProQuad) be used with caution in individuals with a history of cerebral injury, personal or family history of seizures, or any other condition in which fever-induced stress should be avoided.66 The ACIP states that a personal or family (i.e., sibling, parent) history of seizures is a precaution for use of MMRV (ProQuad).72 Studies suggest that children with a personal or family history of febrile seizures or family history of epilepsy are at increased risk for febrile seizures compared with children who do not have such histories.72 ACIP states that children with a personal or family history of seizures generally should receive a dose of MMR and a dose of varicella vaccine (Varivax) because the risks of using MMRV (ProQuad) in these children generally outweigh the benefits.72

Safety and efficacy of MMRV (ProQuad) in HIV-infected individuals not established;27 66 do not use this fixed-combination vaccine in HIV-infected individuals.27 76

Limitations of Vaccine Effectiveness

MMR: May not protect all individuals from measles, mumps, and rubella.1 Safety and efficacy for postexposure prophylaxis following exposure to measles, mumps, or rubella not established.1

MMRV (ProQuad): May not protect all individuals from measles, mumps, rubella, and varicella.66 Safety and efficacy for postexposure prophylaxis after exposure to measles, mumps, rubella, or varicella not established.66

Duration of Immunity

Immunity induced by measles, mumps, and rubella antigens is long-term in most individuals and may be lifelong.8 14 44 52 Although antibody levels may wane, revaccination usually results in an anamnestic immune response.58 60 61

Pre- and Postvaccination Serologic Testing

Prevaccination serologic testing is not required before vaccination unless such testing is considered cost-effective.8 44 46 52 There is no evidence of increased risk of adverse effects if MMR is given to individuals already immune to measles, mumps, and rubella.8 52

When testing for mumps immunity, presence of mumps immunoglobulin G (IgG) by any commonly used serologic assay is acceptable evidence of mumps immunity.44 52 Those with equivocal serologic test results should be considered susceptible to mumps.44 52

The only reliable evidence of previous rubella infection is the presence of rubella IgG antibody.8 44 52 54 Although tests for IgM antibody have been used to diagnose acute and recent rubella infection, IgM tests should not be used to determine rubella immunity since false-positive results can occur.54 Occasionally an individual with a history of documented vaccination against rubella will have negative antibody results; such individuals may receive MMR and do not need to be retested for immunity.52 Those with equivocal serologic test results should be considered susceptible to rubella.44

Postvaccination serologic testing to confirm an immune response after vaccination with MMR is not recommended.44

Concomitant Illness

A decision to administer or delay vaccination in an individual with a current or recent febrile illness depends on the severity of symptoms and etiology of the illness.1 11

ACIP states that minor acute illness, such as mild diarrhea or mild upper respiratory tract infection (with or without fever), generally does not preclude vaccination, but defer vaccination in individuals with moderate or severe acute illness (with or without fever).11

Risk of Neurodevelopmental Disorders

Although it has been theorized that there is a link between the antigens contained in MMR and neurodevelopmental disorders in children (autism),77 78 evidence has been insufficient to support an association between neurodevelopmental disorders and MMR.77 78 79 In 2004, the Immunization Safety Review Committee of the Institute of Medicine (IOM) examined the hypothesis that MMR is causally associated with autism and concluded that the evidence favors rejection of a causal relationship between MMR and autism.78

Tuberculosis

Theoretical risk that measles vaccination might exacerbate untreated tuberculosis.11

MMR and MMRV (ProQuad) are contraindicated in individuals with active untreated tuberculosis.1 66

Defer MMR or MMRV (ProQuad) in patients with active, untreated tuberculosis until antituberculosis therapy has been initiated.1 8 11 66 Tuberculin skin test reactivity in the absence of active tuberculosis is not a contraindication to live, attenuated virus vaccines.11 Tuberculin skin test is not a prerequisite for administration of MMR or MMRV (ProQuad).8 44 66 (See Specific Drugs and Laboratory Tests under Interactions.)

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.1 53

Do not administer MMR or MMRV (ProQuad) that has been mishandled or has not been stored at the recommended temperature.1 53 66 (See Storage under Stability.)

Protect lyophilized and reconstituted vaccine from light at all times;1 53 66 exposure to light may inactivate the vaccine virus.1 53 66

Avoid freezing or exposing the diluent supplied by the manufacturer to freezing temperatures;1 53 66 diluent may be refrigerated or stored at room temperature.1 53 66 (See Storage under Stability.)

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.53

Discard reconstituted MMR vaccine if not used within 8 hours; do not freeze.1 53 Discard reconstituted MMRV (ProQuad) vaccine if not used within 30 minutes; do not freeze.66 (See Storage under Stability.)

Specific Populations

Pregnancy

Category C.1 66

Contraindicated during pregnancy.1 11 44 50 66

Manufacturer states pregnancy should be avoided for 3 months after vaccination.1 66 ACIP, AAP and others state avoid pregnancy for 1 month following vaccination.8 11 52

Routine pregnancy testing before administering MMR not recommended.11 If a pregnant woman is vaccinated or became pregnant within 1–3 months after vaccination, advise her of the theoretical risks to the fetus.1 2 11 44 66 Inadvertent vaccination during pregnancy should not be regarded as a reason to consider termination of pregnancy.11 44

Lactation

Not known whether measles or mumps vaccine virus is distributed into milk.1 Rubella vaccine virus is distributed into milk and may be transmitted to breast-fed infants; infants may have serologic evidence of rubella infection without severe disease.1 Manufacturer recommends caution in nursing women.1

ACIP and AAP state breast-feeding is not a contraindication to MMR since live vaccines appear to pose no special problems for the mother or her nursing infant.8 11 14 44

Pediatric Use

MMR: Safety and efficacy not established in children <6 months of age.1 8

MMRV (ProQuad): Safety and efficacy not established in children <12 months of age or children or adolescents ≥13 years of age.66

Routine immunization against measles, mumps, and rubella is initiated at 12 through 15 months of age.8 44 Infants 6 through 11 months of age may receive MMR if protection against measles is considered necessary (e.g., for measles outbreak control, for travelers).8 9 44 70 Infants <6 months of age usually have partial or complete protection against measles because of maternally derived antibodies.8 44

There is some evidence that infants born to mothers who had wild-type measles may not develop sustained antibody levels if vaccinated at <12 months of age and later revaccinated.1

Geriatric Use

MMR: Clinical studies did not include sufficient numbers of seronegative individuals ≥65 years of age to determine whether these individuals respond differently than younger individuals.1 Other reported clinical experience has not identified differences in responses between geriatric and younger individuals.1

MMRV (ProQuad): Not indicated in adults, including geriatric adults.66

Common Adverse Effects

MMR: Fever,1 31 44 52 transient rash,1 31 44 52 injection site reactions (pain, induration, edema).1 44

MMRV (ProQuad): Adverse effects similar to those reported when varicella vaccine and MMR are administered simultaneously at separate sites,66 but higher incidence of fever (≥38.9°),66 febrile seizures,65 and measles-like rash.66

Interactions for Measles, Mumps, and Rubella Vaccine

Live Vaccines

MMR and MMRV (ProQuad) are live, attenuated virus vaccine.1 11 66 Some oral live vaccines (e.g., rotavirus vaccine live oral, typhoid vaccine live oral, poliovirus vaccine live oral (OPV; no longer commercially available in the US) can be administered simultaneously with or at any interval before or after MMR or MMRV (ProQuad).1 8 11 However, because of theoretical concerns that the immune response to intranasal live vaccines or other parenteral live virus vaccines might be impaired if given within 28–30 days of another live virus vaccine, if MMR and intranasal or parenteral live vaccines are not administered on the same day, they should be administered at least 4 weeks (i.e., 28 days) apart to minimize the potential for interference.1 8 11 (See Specific Drugs and Laboratory Tests under Interactions.)

Inactivated Vaccines and Toxoids

MMR or MMRV (ProQuad) may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after inactivated vaccines, recombinant vaccines, polysaccharide vaccines, or toxoids.11 14 44 66 (See Specific Drugs and Laboratory Tests under Interactions.)

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Blood products (e.g., whole blood, packed RBCs, plasma)

Antibodies contained in blood products may interfere with the immune response to MMR or MMRV (ProQuad)8 11 44 66

Do not administer MMR simultaneously with or for specified intervals before or after administration of blood products8 11 44

Defer MMR for ≥3 months following administration of RBCs (with adenine-saline added); for ≥6 months following administration of packed RBCs or whole blood; or for ≥7 months following administration of plasma or platelet products11

After administering MMR, avoid blood products for 2 weeks; if use of a blood product is considered necessary during this period, give a repeat vaccine dose after the recommended interval unless serologic testing is feasible and indicates a response to the vaccine was attained11

Diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed (DTaP), tetanus and reduced diphtheria toxoids and acellular pertussis vaccines adsorbed (Tdap)

MMR or MMRV (ProQuad) may be administered concurrently (using different syringes and different injection sites) or at any interval before or after DTaP or Tdap1 11 44 66

Haemophilus b (Hib) vaccine

Simultaneous administration of MMR and Hib vaccine does not interfere with the immune response or increase adverse effects of either vaccine1 14

MMR or MMRV (ProQuad) may be administered simultaneously (using different syringes and different injection sites) or at any time before or after Hib vaccine11 14 44 55 66

Hepatitis B (HepB) vaccine

Although specific studies not available, HepB vaccine is an inactivated vaccine and interactions are not expected11

MMR or MMRV (ProQuad) may be administered simultaneously (using different syringes and different injection sites) or at any interval before or after HepB vaccine11 66

Immune globulin (IGIM, IGIV) or specific immune globulin (HBIG, RIG, TIG, VZIG)

Antibodies contained in immune globulin preparations may interfere with the immune response to MMR or MMRV (ProQuad)1 8 11 15 31 44 66

MMR should not be administered simultaneously with or for specified intervals before or after administration of immune globulin preparations1 8 11 31

Defer administration of MMR for ≥3 months following administration of tetanus immune globulin (TIG), hepatitis B immune globulin (HBIG), or immune globulin IM (IGIM) used for postexposure prophylaxis of hepatitis A virus (HAV); for ≥4 months following administration of rabies immune globulin (RIG); for ≥5 months following administration of IGIM used for measles prophylaxis in immunocompetent individuals; for ≥6 months following administration of cytomegalovirus immune globulin IV (CMV-IGIV) or IGIM for measles prophylaxis in immunocompromised individuals; for ≥8 months following administration of immune globulin IV (IGIV) for replacement therapy of immunodeficiencies or VZIG or IGIV for postexposure prophylaxis of severe varicella; for ≥8–10 months following administration of IGIV for treatment of idiopathic thrombocytopenic purpura (ITP); or for ≥11 months following administration of IGIV for Kawasaki syndrome8 11 31

If MMR is administered simultaneously with an immune globulin preparation or were administered at less than the recommended interval, consider that vaccine-induced immunity may be compromised; give an additional vaccine dose after the specified interval unless serologic testing is feasible and indicates a response to the vaccine was attained8 11 31

After administering MMR or MMRV (ProQuad), avoid immune globulin preparations for 2 weeks; if use of an immune globulin is considered necessary during this period, give a repeat vaccine dose after the recommended interval unless serologic testing is feasible and indicates a response to the vaccine was attained11

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, radiation)

Use of MMR or MMRV (ProQuad) in individuals receiving immunosuppressive therapy may result in more extensive vaccine-associated rash or disseminated disease1 27 66

Corticosteroid therapy (prednisone or equivalent) in a dosage ≥2 mg/kg daily or ≥20 mg daily given for ≥2 weeks is considered immunosuppressive11 31 44

Short-term (<2 weeks), low- to moderate-dose systemic corticosteroid therapy; long-term, alternate-day systemic corticosteroid therapy using low to moderate doses of short-acting drugs; topical corticosteroid therapy (e.g., nasal, cutaneous, ophthalmic); or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive in usual dosages8

Defer vaccination with MMR or MMRV (ProQuad) until immunosuppressive therapy is discontinued8 15 31 44

Optimum interval between discontinuance of immunosuppressive therapy and subsequent administration of a live viral vaccine has not been determined;15 31 44 live viral vaccines generally should not be administered for at least 3 months after immunosuppressive therapy is discontinued15 31 44

In patients who received corticosteroid therapy that is considered immunosuppressive,44 delay administration of MMR for at least 3 months after the corticosteroid is discontinued44

Manufacturer states MMR or MMRV (ProQuad) may be used in patients receiving corticosteroids as replacement therapy (e.g., Addison’s disease)1 2 3 4 66

Influenza vaccine

Intranasal live influenza vaccine: Simultaneous administration with MMR vaccine in children 12 through 15 months of age did not interfere with the immune response to any vaccine component and did not increase the frequency of adverse effects67

Parenteral inactivated influenza vaccine: Since this influenza vaccine is an inactivated vaccine, interactions with live vaccines such as MMR or MMRV (ProQuad) are unlikely11

Intranasal live influenza vaccine: If not given simultaneously, give at least 4 weeks apart, if possible11

Parenteral inactivated influenza vaccine: May be administered simultaneously (using different syringes and different injection sites) or at any interval before or after MMR11

Pneumococcal vaccine

Concomitant administration of PCV7 (Prevnar) or PPSV23 (Pneumovax 23) and MMR did not result in reduced antibody response to MMR8 68

Concomitant administration of PCV7 (Prevnar) and MMRV (ProQuad) did not result in reduced antibody response to MMR66

Pneumococcal vaccine may be administered concurrently (using different syringes and different injection sites) or at any interval before or after MMR or MMRV (ProQuad)47 48 66

Poliovirus vaccine inactivated (IPV)

Simultaneous administration of MMR and IPV does not interfere with the immune response or increase adverse effects of either vaccine11

MMR may be administered concurrently (using different syringes and different injection sites) or any time before or after IPV11 44

Rho(D) immune globulin

Specific studies not available evaluating whether passively acquired antibodies from Rho(D) immune globulin interfere with the immune response to MMR11

Because of the importance of postpartum rubella vaccination in women who do not have evidence of immunity, vaccination of such women should not be delayed because they received Rho(D) immune globulin;11 if possible, test for serologic evidence of immunity ≥3 months after vaccination11

Rotavirus vaccine

No evidence to date that parenterally administered live vaccines such as MMR interfere with the immune response to rotavirus vaccine11

May be administered concomitantly with or at any interval before or after MMR11

Test, Tuberculin

MMR may temporarily suppress tuberculin skin sensitivity1 8 11 44 76

Tuberculin tests (if required) should be administered before, simultaneously with, or at least 4–6 weeks after administration of MMR or MMRV (ProQuad)1 8 44 66 76

Typhoid vaccine

Oral live typhoid vaccine (Vivotif): Specific data not available regarding immunogenicity when administered concurrently or within 30 days of MMR11 69

Parenteral inactivated typhoid vaccine (Typhim Vi): Since this typhoid vaccine is an inactivated vaccine, interactions with live vaccines such as MMR are unlikely11

Oral live typhoid vaccine (Vivotif): Do not delay administration of typhoid vaccine if warranted11 69

Parenteral inactivated typhoid vaccine (Typhim Vi): May be administered simultaneously (using different syringes and different injection sites) or at any interval before or after MMR11

Varicella vaccine

Simultaneous administration of monovalent varicella vaccine and MMR does not interfere with the immune response to either vaccine;1 6 11 27 44 varicella vaccine may be less effective if given <30 days after MMR6 11

The fixed-combination vaccine containing MMR and varicella vaccine (MMRV; ProQuad) results in antibody responses similar to those obtained after simultaneous administration of a single dose of MMR and a single dose of Varivax;51 incidence of febrile seizures in children 12–60 months of age after a dose of MMRV (ProQuad) is higher than that reported when a dose of MMR and a dose of varicella vaccine are given during a single health-care visit66

MMR and varicella vaccine may be given simultaneously (using different syringes and different injection sites);6 11 44 if not administered simultaneously, give at least 1 month apart6

Alternatively, fixed-combination vaccine containing MMR and varicella vaccine (MMRV; ProQuad) may be used in children 12 months through 12 years of age when a dose of MMR and a dose of varicella vaccine is indicated in this age group11 27 66

Yellow fever vaccine

Yellow fever vaccine has been administered simultaneously with monovalent measles vaccine (no longer commercially available in the US) without an increase in adverse effects or interference with the immune response to the vaccine11

Effect of nonsimultaneous administration of yellow fever vaccine and MMR unknown11

MMR and yellow fever vaccine may be administered simultaneously (using different syringes and different injection sites)11 44

If not given simultaneously, give at least 4 weeks apart11

Stability

Storage

Parenteral

For injection, for Sub-Q Use (MMR)

Store lyophilized MMR at 2–8°C or colder.1 53 Maintain a temperature of ≤10°C during shipment.1 53 Freezing during shipment or storage does not affect potency.1

Protect from light during shipment and storage to maintain potency.1 53

Store diluent provided by the manufacturer either at room temperature (20–25°C) or in a refrigerator (2–8°C); do not freeze.1 53

After reconstitution, use as soon as possible.1 53 May be stored for up to 8 hours in a dark place at 2–8°C; discard if not used within 8 hours.1 53

MMR and the diluent provided by the manufacturer do not contain thimerosal or any other preservatives.1

For Injection, for Sub-Q Use (MMRV; ProQuad)

To maintain potency, lyophilized MMRV (ProQuad) must be kept frozen at -15°C or colder and protected from light during shipment and storage.53 66 Must be shipped in insulated containers with dry ice and delivered within 2 days.53

After delivery, keep lyophilized vaccine frozen at -15°C or colder and protect from light; any freezer (e.g., chest, frost-free) that reliably maintains an average temperature of -15°C or colder and has a separate sealed freezer door is acceptable.53 66

When optimal handling conditions are not feasible (e.g., during transportation to off-site clinics, unavailability of dry ice), potency can be maintained if vials of lyophilized vaccine are stored for ≤72 hours at 2–8°C.53 66

Discard any vials of lyophilized vaccine that have been stored at 2–8°C for >72 hours.53 66 Contact manufacturer at 800-637-2590 for information regarding vaccine stability under conditions other than those recommended.53 66

Store diluent provided by the manufacturer separately, either at room temperature (20–25°C) or in a refrigerator (2–8°C);53 66 do not freeze.53

To minimize loss of potency and ensure an adequate immunizing dose, use MMRV (ProQuad) immediately after reconstitution; discard any reconstituted vaccine not used within 30 minutes.66

Do not freeze reconstituted MMRV (ProQuad).66

MMRV (ProQuad) does not contain thimerosal or any other preservatives.66

Actions

  • MMR is a fixed-combination preparation containing measles, mumps, and rubella virus vaccines live.1 Antigens contained in MMR are identical to those contained in monovalent measles, mumps, and rubella virus vaccines (monovalent vaccines no longer commercially available in the US).1

  • MMR also is commercially available in the US as a fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad).66

  • MMR stimulates active immunity to measles, mumps, and rubella by inducing production of specific IgG and IgM antibodies.1 11 52 MMRV (ProQuad) stimulates active immunity to measles, mumps, rubella, and varicella by inducing production of specific antibodies.66

  • Vaccination with MMR produces an inapparent or mild, noncommunicable infection followed by antibody production.44 Vaccine-induced antibody titers generally are lower than those stimulated by natural measles, mumps, or rubella infection.14 44

  • Individuals who fail to respond to the first dose of MMR generally respond to a second dose.44 52

  • A single dose of MMR results in measles antibody in approximately 95% of children who receive the dose at 12 months of age and 98% of those who receive the dose at 15 months of age.8 44 52 Following a second dose given at least 4 weeks after the first, >99% of individuals have evidence of measles immunity.8 44 52

  • A single dose of MMR is 75–95% effective in preventing mumps.10 44 Substantially higher levels of protection occur following a second dose.10

  • A single dose of MMR given at ≥12 months of age results in production of rubella antibody and protection against clinical and symptomatic infection in >90–95% of vaccinees.8 14 44 52

  • Clinical studies in healthy children 12–23 months of age indicate that those who received a single dose of MMRV (ProQuad) developed antibody levels against measles, mumps, rubella, and varicella that were similar to levels attained in children who received a single dose of MMR and a single dose of varicella vaccine (Varivax) concomitantly at separate sites.66

Advice to Patients

  • Prior to administration of each vaccine dose, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative as required by the National Childhood Vaccine Injury Act (VISs are available at ).1 13 66

  • Advise patient and/or patient’s parent or guardian of the risks and benefits of vaccination against measles, mumps, and rubella.1

  • Importance of receiving the complete immunization series (2 doses in children and adolescents, 1 or 2 doses in adults) to ensure highest level of protection against measles, mumps, and rubella.1 5 8 52

  • Advise patient that MMR may not provide protection in all vaccinees.1

  • Advise postpubertal females receiving MMR that arthralgia and/or arthritis may occur 2–4 weeks after vaccination and that joint symptoms usually are self-limited.1

  • Advise patient they should not receive MMR if they have a disease that weakens the immune system (e.g., cancer, HIV/AIDS) or are receiving treatment that may weaken the immune system (e.g., cancer treatment with radiation or drugs, corticosteroids).1

  • Importance of contacting clinicians if a hypersensitivity reaction (difficulty breathing, hoarseness, wheezing, hives, paleness, weakness, fast heart beat, dizziness) or other moderate or severe reaction (high fever, behavior changes) occur following a dose.13 Clinicians or individuals can report any adverse reactions that occur following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or .1 13

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise women to avoid pregnancy for 1–3 months following a dose of MMR.1 13

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

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

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

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

M-M-R II

Merck

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

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

Measles Virus Vaccine Live (More Attenuated Enders’ Line) ≥3 log 10 tissue culture infective dose 50% (TCID50), Mumps Virus Vaccine Live (Jeryl Lynn [B level] Strain) ≥4.3 log10 TCID50, Rubella Virus Vaccine Live (Wistar RA 27/3 Strain) ≥3 log 10 TCID50, and Varicella Virus Vaccine Live (Oka/Merck Strain) ≥3.99 log 10 plaque-forming units (PFU) per 0.5 mL

ProQuad

Merck

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

1. Merck & Company. M-M-R II (measles, mumps, and rubella virus vaccine live) prescribing information. Whitehouse Station, NJ; 2009 Sep.

2. Merck & Company. Attenuvax (measles virus vaccine live) prescribing information. Whitehouse Station, NJ; 2006 Feb.

3. Merck & Company. Meruvax II (rubella virus vaccine live) prescribing information. Whitehouse Station, NJ; 2006 Feb.

4. Merck & Company. Mumpsvax (mumps virus vaccine live) Jeryl Lynn strain prescribing information. Whitehouse Station, NJ; 2002 Sept.

5. Centers for Disease Control and Prevention. Recommended immunization schedules for persons 0 through 18 years–United States, 2010. MMWR Morb Mortal Wkly Rep. 2010; 59.

6. Centers for Disease Control and Prevention. Simultaneous administration of varicella vaccine and other recommended childhood vaccines—United States, 1995-1999. MMWR Morb Mortal Wkly Rep. 2001; 50:1058-61. [IDIS 473729] [PubMed 11808928]

7. Watson BM, Laufer DS, Kuter BJ et al. Safety and immunogenicity of a combined live attenuated measles, mumps, rubella, and varicella vaccine (MMRIIV) in healthy children. J Infect Dis. 1996; 173:731-4. [IDIS 364240] [PubMed 8627041]

8. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

9. Centers for Disease Control and Prevention. Health information for international travel, 2010. Atlanta, GA: US Department of Health and Human Services; 2010. Updates available from CDC website ().

10. Centers for Disease Control and Prevention. Notice to readers: Updated recommendations of the Advisory Committee on Immunization Practices (ACIP) for the control and elimination of mumps. MMWR Morb Mortal Wkly Rep. 2006; 55:629-30. [PubMed 16761359]

11. Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-15):1-47.

13. Centers for Disease Control and Prevention. Measles, mumps & rubella (MMR) vaccine information statement. 2008 Mar 13. From CDC website.

14. Centers for Disease Control Immunization Practices Advisory Committee (ACIP). Rubella prevention: recommendations of the immunization practices advisory committee. MMWR Recomm Rep. 1990; 39(RR-15):1-18.

15. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence. MMWR Recomm Rep. 1993; 42(RR-4):1-18.

16. Committee on Infectious Diseases. Recommended timing of routine measles immunization for children who have recently received immune globulin preparations. Pediatrics. 1994; 93:682-5. [IDIS 327896] [PubMed 8134232]

17. Lavi S, Zimmerman B, Koren G et al. Administration of measles, mumps, and rubella virus vaccine (live) to egg-allergic children. JAMA. 1990; 263:269-71. [IDIS 262057] [PubMed 2294292]

18. Trotter AC, Stone BD, Laszlo DJ et al. Measles, mumps, rubella vaccine administration in egg-sensitive children: systemic reactions during vaccine desensitization. Ann Allergy. 1994; 72:25-8. [IDIS 325128] [PubMed 8291745]

19. Puvvada L, Silverman B, Bassett C et al. Systemic reactions to measles-mumps-rubella vaccine skin testing. Pediatrics. 1993; 91:835-6. [IDIS 312313] [PubMed 8464677]

20. James JM, Burks AW, Roberson PK et al. Safe administration of the measles vaccine to children allergic to eggs. N Engl J Med. 1995; 332:1262-6. [IDIS 346533] [PubMed 7708070]

21. Fasano MB, Wood RA, Cooke SK et al. Egg hypersensitivity and adverse reactions to measles, mumps, and rubella vaccine. J Pediatr. 1992; 120:878-81. [IDIS 297893] [PubMed 1593346]

22. Kemp A, Van Asperen P, Mukhi A. Measles immunization in children with clinical reactions to egg protein. Am J Dis Child. 1990; 144:33-5. [IDIS 264152] [PubMed 2294717]

23. Bruno G, Giampietro PG, Grandolfo ME et al. Safety of measles immunisation in children with IgE-mediated egg allergy. Lancet. 1990; 335:739. [IDIS 265055] [PubMed 1969103]

24. Aickin R, Hill D, Kemp A. Measles immunisation in children with allergy to egg. BMJ. 1994; 309:223-5. [IDIS 333177] [PubMed 8069138]

25. Beck SA, Williams LW, Shirrell A et al. Egg hypersensitivity and measles-mumps-rubella vaccine administration. Pediatrics. 1991; 88:913-7. [IDIS 291323] [PubMed 1945631]

26. Greenberg MA, Birx DL. Safe administration of mumps-measles-rubella vaccine in egg-allergic children. J Pediatr. 1988; 113:504-6. [IDIS 246076] [PubMed 3411397]

27. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007; 56(RR-4):1-40.

28. King GE, Markowitz LE, Heath J et al. Antibody response to measles-mumps-rubella vaccine of children with mild illness at the time of vaccination. JAMA. 1996; 275:704-7. [IDIS 360966] [PubMed 8594268]

29. Dennehy PH, Saracen CL, Peter G. Seroconversion rates to combined measles-mumps-rubella-varicella vaccine of children with upper respiratory tract infection. Pediatrics. 1994; 94:514-6. [IDIS 336758] [PubMed 7936862]

30. Ratnam S, West R, Gadag V. Measles and rubella antibody response after measles-mumps-rubella vaccination in children with afebrile upper respiratory tract infection. J Pediatr. 1995; 127:432-4. [IDIS 354203] [PubMed 7658276]

31. Centers for Disease Control and Prevention. Update: vaccine side effects, adverse reactions, contraindications, and precautions. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1996; 45(RR-12):1-35.

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