Mumps Virus Vaccine Live (Monograph)

Drug class: Vaccines
ATC class: J07BE01
VA class: IM100

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

Introduction

Mumps virus vaccine live is a preparation of live, attenuated organisms of the Jeryl Lynn (B level) strain of mumps virus that stimulates active immunity to mumps infection.¹¹⁰ Mumps virus vaccine live is commercially available as a fixed-combination vaccine containing mumps, measles, and rubella antigens (MMR; M-M-R II)¹⁰⁴ and as a fixed-combination vaccine containing mumps, measles, rubella, and varicella antigens (MMRV; ProQuad).¹⁶⁸

Uses for Mumps Virus Vaccine Live

Mumps virus vaccine live is used to stimulate active immunity to mumps.¹¹⁰ Monovalent mumps virus vaccine live (Mumpsvax) is no longer commercially available in the US.¹⁷⁹ Mumps virus vaccine live is commercially available in the US as a fixed-combination vaccine containing measles, mumps, and rubella antigens (MMR; M-M-R II) for use in adults, adolescents, and children 12 months of age or older¹⁰⁴ and as a fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad) for use in children 12 months through 12 years of age.¹⁶⁸

The US Public Health Service Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP) recommend universal immunization against mumps for all susceptible children, adolescents, and adults, unless mumps virus vaccine live is contraindicated.^{100 102 162 163 169} (See Cautions: Precautions and Contraindications.)

The ACIP, AAP, and AAFP state that the fixed-combination vaccine containing measles, mumps, and rubella vaccine live (MMR) is preferred over monovalent mumps virus vaccine live (no longer commercially available in the US) for both primary immunization and revaccination to assure immunity to all 3 diseases.^{102 116 162 163} Alternatively, in children 12 months through 12 years of age when a dose of MMR and a dose of varicella virus vaccine live are indicated for primary immunization, use of the fixed-combination vaccine containing MMR and varicella virus vaccine live (MMRV; ProQuad) can be considered.^{168 170}

A killed mumps virus vaccine was available in the US from 1950–1978, and while this vaccine induced antibody to the mumps virus, the resultant mumps immunity was transient.¹⁶² Therefore, individuals who previously received killed mumps virus vaccine may benefit from revaccination with MMR.

Adults born before 1957 are likely to have been infected naturally with mumps and generally can be considered immune, even if they did not have clinically recognizable disease.^{100 102 162 171} Other individuals can be considered immune to mumps if there is documentation of adequate immunization against mumps (2 doses of MMR or mumps virus-containing vaccine for school aged-children in grades K-12, college students, health-care personnel, international travelers; at least 1 dose in preschool-aged children, adults not at high risk), physician-diagnosed natural mumps infection, or serologic evidence of mumps immunity.^{100 162 169 171} Adults born in 1957 or later who lack adequate documentation of immunity should receive 1 dose of MMR to provide immunity against mumps, unless MMR is contraindicated.¹⁶⁹

Individuals with an equivocal serologic test should be considered susceptible to mumps unless they have other evidence of mumps immunity or a subsequent serologic test indicates mumps immunity.¹⁶² The demonstration of mumps immunoglobulin G (IgG) by any commonly used serologic assay is acceptable evidence of mumps immunity.^{162 174} It is not necessary to test for susceptibility prior to administration of MMR since there is no evidence that individuals already immune because of previous vaccination or natural disease are at any unusual risk of local or systemic reactions to the vaccine.¹⁷⁹ Any individual who is unsure about their mumps disease history and/or mumps vaccination history should be vaccinated with MMR.¹⁰⁰

Primary Immunization

Infants and Children 12 Months through 12 Years of Age

For routine primary immunization in children, the ACIP, AAP, and AAFP recommend that the first dose of MMR be given at 12 through 15 months of age.^{102 116 162 163} The vaccine should not be administered to children younger than 12 months of age solely for mumps protection, because most infants have maternal antibodies which may prevent a satisfactory immunologic response to the vaccine; however, vaccination with MMR aimed at preventing measles occasionally may be warranted in children as young as 6 months of age in certain situations associated with increased risk of exposure to measles virus (e.g., during measles outbreaks, travel to areas with increased risk of measles).¹¹¹ If a live mumps virus-containing vaccine was administered to a child younger than 12 months of age, the child may benefit from revaccination with MMR after reaching 12 months of age.

To improve control of measles, mumps, and rubella, a second dose of MMR is recommended for routine immunization in children.^{102 116 119 161 162 171} The second dose preferably should be given at 4 through 6 years of age (just prior to entry into kindergarten or first grade), but may be given earlier during any routine visit provided at least 4 weeks (i.e., at lest 28 days) have elapsed since the first dose and both the first and second doses are administered beginning at or after 12 months of age.^{102 162 163} Those who have not previously received the second MMR dose should complete the vaccination schedule by 11–12 years of age (just prior to entry into middle or junior high school).^{162 163} If MMR is administered to infants before their first birthday, they should be considered unimmunized for the purposes of determining the need for further vaccination; they should be revaccinated with a 2-dose regimen of MMR initiated at 12 months of age.¹⁶²

The ACIP, AAP, and AAFP state that primary immunization against mumps, measles, and rubella can be integrated with primary immunization against diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, influenza, pneumococcal disease, poliomyelitis, and varicella.^{100 102 103 116 120 121 122 123 124 125 126 166 167} In general, simultaneous administration (on the same day) of the most widely used vaccines, including diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP), Hib conjugate vaccine, MMR, poliovirus vaccine inactivated (IPV), and varicella virus vaccine live, has resulted in seroconversion rates and adverse effects similar to those observed when the vaccines were administered separately.^{102 103 116} Therefore, the ACIP, AAP, and AAFP recommend simultaneous administration of all vaccines appropriate for the age and previous vaccination status of the recipient, including DTaP, Hib conjugate vaccine, hepatitis A vaccine, hepatitis B vaccine, influenza vaccine, MMR, pneumococcal vaccine, IPV, and varicella virus vaccine live, especially if an individual is unlikely to return for further vaccination.^{100 102 103 116 120 121 122 123 124 125 126 161} (See Drug Interactions: Vaccines.)

Internationally Adopted Children and Other Immigrants

Individuals seeking an immigrant visa for permanent US residency must provide proof of age-appropriate vaccination according to the US Recommended Childhood and Adolescent Immunization Schedules or the US Recommended Adult Immunization Schedule.^{111 116} Although this vaccination requirement applies to all immigrant infants and children entering the US, internationally adopted children younger than 11 years of age are exempt from the overseas vaccination requirements; however, adoptive parents are required to sign a waiver indicating their intention to comply with the vaccination requirements within 30 days after the infant or child arrives in the US.¹¹¹ The CDC states that more than 90% of newly arrived internationally adopted children need catch-up vaccinations to meet the US Recommended Immunization Schedules.¹¹¹

The fact that immunization schedules of other countries may differ from US schedules (e.g., different recommended vaccines, recommended ages of administration, and/or number and timing of vaccine doses) should be considered.¹¹⁶ Vaccines administered outside the US can generally be accepted as valid if the administration schedule was similar to that recommended in the US childhood and adolescent immunization schedules.¹¹⁶ Only written vaccination records should be considered as evidence of previous vaccination since such records are more likely to accurately predict protection if the vaccines administered, intervals between doses, and child’s age at the time of vaccination are similar to US recommendations; however, the extent to which an internationally adopted child’s immunization record reflects their protection against disease is unclear and it is possible there may be transcription errors in such records (e.g., single-antigen vaccine may have been administered although a multiple-antigen vaccine was recorded).¹¹⁶ Although vaccines with inadequate potency have been produced in other countries, most vaccines used worldwide are immunogenic and produced with adequate quality control standards.¹¹⁶

When the immune status of an internationally adopted child is uncertain, the ACIP recommends that health-care providers either repeat vaccinations (since this usually is safe and avoids the need to obtain and interpret serologic tests) and/or use selective serologic testing to determine the need for immunizations (helps avoid unnecessary injections).¹¹⁶ MMR is not used in most countries.¹¹¹ Therefore, although serologic testing is available to verify immunization status in children 12 months of age or older,^{111 116} the CDC states that administration of MMR is preferable to serologic testing unless there is documentation that the child has had mumps.¹¹¹ The ACIP states that the recommended approach is to revaccinate an internationally adopted child with 1 or 2 doses of MMR (depending on the child’s age) without regard to the child’s prior vaccination record since serious adverse effects after MMR vaccination are rare and there is no evidence that administration of MMR increases the risk for adverse reactions among individuals already immune to measles, mumps, or rubella.¹¹⁶

Adolescents and Adults

During the late 1980s, there was in increase in the reported prevalence of mumps in unvaccinated middle and high school students and mumps outbreaks were reported at universities and colleges and other places where young adults congregate.¹⁰⁹ In addition, data from the late 1980s and early 1990s indicate that mumps outbreaks were occurring in schools with extremely high (more than 95%) vaccination coverage, suggesting that a single dose of mumps virus vaccine live or MMR was not sufficient to prevent mumps outbreaks in school settings.¹⁷¹ Therefore, the ACIP now states that adequate immunization of adults at high risk (e.g., health-care personnel, international travelers, students at college or other post-high school educational institutions) is defined as 2 doses of a mumps virus-containing vaccine.¹⁷¹ Mumps infection during adulthood is likely to produce more severe disease, including orchitis.¹⁰² Although fatalities related to mumps are rare, death resulting from mumps and its complications occurs most often in adults.¹⁰²

Adolescents 11–12 Years of Age

The ACIP, AAP, and AAFP recommend that any adolescent who has not previously received a second dose of MMR receive the dose during a routine preadolescent preventive health-care visit at 11–12 years of age.^{102 161 162 163} This routine health-care visit provides an opportunity to administer “catch-up” vaccines that were missed at an earlier age, administer vaccines routinely recommended at 11–12 years of age, administer vaccines recommended for certain high-risk adolescents, schedule future appointments that may be necessary to complete recommended immunization schedules, and provide adolescents with other recommended preventive health services such as guidance on health behaviors and screening for biomedical, behavioral, and emotional conditions.^{102 161 162} During the health-care visit at 11–12 years of age, the vaccination history of the adolescent should be assessed.^{102 161 162} If the adolescent does not have information regarding their vaccination history, the health-care provider should attempt to obtain such information through documentation from the parent, previous providers, or school records.¹⁶¹ When documentation of an adolescent’s vaccination status is not available at the time of the preventive health-care visit, an assumption can be made that the adolescent has received those vaccines required by state laws and regulations that have been in effect for some time (e.g., those required on entry to kindergarten) and these vaccines can be withheld while awaiting documentation.¹⁶¹ However, vaccine doses recommended for adolescents that were not included in previous laws and recommendations should be administered.¹⁶¹

Ideally, all vaccines routinely indicated at 11–12 years of age should be administered during the initial adolescent visit (MMR, hepatitis B vaccine, tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap), varicella virus vaccine live).¹⁶¹ However, since multiple doses of some vaccines are required to complete primary immunization and because simultaneous administration of a large number of vaccines may be indicated in some adolescents, providers may need to be flexible in determining which vaccines to administer during the initial visit and which to schedule for return visits.¹⁶¹ While specific studies evaluating the safety and efficacy of simultaneous administration of vaccines in adolescents are not available, there is extensive evidence from clinical studies and experience in infants and children that simultaneous administration of the most widely used vaccines does not decrease the antibody response or increase adverse reactions to these vaccines.¹⁶¹ In circumstances where multiple vaccines (i.e., 4 or more) are indicated in adolescents 11–12 years of age, the provider may choose to defer some vaccines for administration during one or more future visits; however, the vaccines should be prioritized based on which require multiple doses, which diseases pose an immediate threat to the adolescent, and whether the adolescent is likely to return for scheduled visits.¹⁶¹ During any subsequent visits, the adolescent’s vaccination status should be rechecked and any deficiencies corrected.¹⁶¹

HIV-infected Individuals

MMR can be used in adults, adolescents, or children with human immunodeficiency virus (HIV) infection who do not have evidence of severe immunosuppression.^{102 127 142 162 164 182}

The ACIP, AAP, US Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society, and others state that all asymptomatic HIV-infected children, adolescents, and adults should receive MMR according to the usually recommended immunization schedules.^{102 127 162 164 182} 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.^{102 127 162 164 182} Because the immunologic response to vaccines may decrease as HIV disease progresses, vaccination early in the course of HIV infection may be more likely to induce an immune response; in addition, approximately 5% of HIV-infected infants born in the US will be severely immunocompromised at 12 months of age.¹⁶² Therefore, the ACIP and other experts recommend that HIV-infected infants who are not severely immunocompromised receive MMR as soon as possible upon reaching their first birthday (i.e., at 12 months of age) and consideration should be given to administering the second dose of MMR as soon as 1 month (i.e., at least 28 days) after the first dose.^{142 162 182}

MMR is contraindicated in HIV-infected individuals with severe immunosuppression (i.e., children younger than 12 months of age with CD4⁺ T-cell count less than 750/mm³; children 1 through 5 years of age with CD4⁺ T-cell count less than 500/mm³; children 6 years of age or older, adolescents, and adults with CD4⁺ T-cell count less than 200/mm³; children younger than 13 years of age with CD4⁺ T-cell percentage less than 15%).^{102 127 142 162 164 182} (See Individuals with Altered Immunocompetence under Cautions: Precautions and Contraindications.)

The serologic response to vaccines (including MMR) may be reduced in some HIV-infected patients and may be inversely correlated with the severity of the disease.¹⁰⁷ In addition, MMR may be ineffective in HIV-infected individuals who have received high-dose IV immune globulin therapy (e.g., for the prevention of serious bacterial infections) within the 3 months preceding administration of the vaccine.^{119 162} (See Drug Interactions: Immune Globulins.)

MMR may be given to any family member residing in the household or any close contact of an HIV-infected patient since extensive experience has shown that live, attenuated MMR vaccine viruses are not transmitted from vaccinated individuals to others.¹⁶²

Health-care Personnel

Because transmission of mumps has occurred in medical settings, the ACIP recommends that all individuals who work in health-care facilities have adequate documentation of mumps vaccination or immunity (i.e., documentation of vaccination with 2 doses of mumps virus-containing vaccine with the first dose given on or after 12 months of age and the second dose given at least 28 days after the first dose, laboratory evidence of immunity, or laboratory confirmation of disease).^{171 165 174 180} Those who have received only 1 dose of a mumps virus-containing vaccine should receive a dose of MMR (provided it has been at least 4 weeks [i.e., at least 28 days] since the first dose).^{171 180}

Although birth before 1957 generally is considered acceptable evidence of mumps immunity, health-care facilities should consider recommending 2 doses of MMR to unvaccinated workers born before 1957 who do not have laboratory evidence of mumps immunity or laboratory confirmation of disease.¹⁸⁰

Sporadic nosocomial cases of mumps have occurred in long-term care facilities housing adolescents and young adults.¹⁶² Mumps virus is less transmissible than measles or other respiratory viruses, and low levels of mumps transmission in the community result in a low risk of introduction of the disease into health-care facilities.¹⁶² Nonetheless, an effective routine MMR vaccination program for health-care workers is the best approach for preventing nosocomial transmission since mumps virus is shed by infected individuals before clinical symptoms become evident and many infected individuals remain asymptomatic.^{162 171}

Travelers

Although vaccination against mumps is not a requirement for entry into any country, susceptible individuals, particularly children approaching puberty, adolescents, and adults, traveling or living abroad should be immunized against the disease, unless the vaccine is contraindicated.^{102 111 162} The risk for exposure to mumps outside the US is high.¹¹¹ Mumps virus is endemic in many countries throughout the world; mumps vaccine is used in only 57% of World Health Organization (WHO) member countries.¹¹¹

The ACIP and CDC state that adequate vaccination against mumps for international travelers is defined as 2 doses of a vaccine containing mumps virus vaccine live.^{111 171} Because the risk of serious disease from natural mumps infection is small in infants, administration of MMR to travelers younger than 12 months of age is unnecessary unless protection against measles is indicated.^{102 111}

Postexposure Vaccination

In individuals who have been exposed to natural mumps virus, there is no evidence that administration of a mumps virus-containing vaccine would prevent infection; however, if exposure did not result in infection, postexposure vaccination may be given to provide protection against subsequent infection.^{102 162 174} There is no increased risk associated with administration of a mumps virus-containing vaccine during the incubation period of the disease.¹⁰² Because about 90% of adults who have no knowledge of past infection are immune by serologic testing, postexposure vaccination is not routinely indicated for individuals born prior to 1957 unless they are known to be seronegative;¹⁰² however, vaccination of such individuals also is not precluded and can be undertaken in outbreak settings.¹⁶²

During a mumps outbreak, the ACIP recommends that consideration be given to administering a second dose of MMR 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).¹⁷¹ In addition, in an outbreak setting, the ACIP states that health-care facilities should strongly consider recommending 2 doses of MMR to unvaccinated personnel born before 1957 unless they have laboratory evidence of immunity or laboratory confirmation of disease.^{171 174 180}

Mumps Virus Vaccine Live Dosage and Administration

Reconstitution and Administration

The fixed-combination vaccine containing measles, mumps, and rubella antigens (MMR; M-M-R II) is administered by subcutaneous injection.¹⁰⁴ The vaccine should not be administered IV.¹⁰⁴

MMR is reconstituted by adding the entire amount of diluent supplied by the manufacturer to the vial of lyophilized vaccine and agitating the vial.¹⁰⁴ Only the diluent provided by the manufacturer should be used.¹⁰⁴ The preparation should be discarded if the lyophilized vaccine does not dissolve completely.¹⁰⁴

Reconstituted MMR should be inspected visually for particulate matter and discoloration prior to administration.¹⁰⁴ The vaccine should be reconstituted and administered using sterile syringes and needles that are free of preservatives, antiseptics, and detergents, since these substances may inactivate live virus vaccines.¹⁰⁴

To minimize loss of potency and ensure an adequate immunizing dose, MMR should be administered immediately following reconstitution.¹⁰⁴ (See Chemistry and Stability: Stability.)

The preferred site for subcutaneous injection of MMR is the upper-outer triceps area; injections also can be given into the anterolateral thigh.^{104 116} For children 1 year of age and older, adolescents, and adults, the upper-outer triceps area usually is preferred.¹¹⁶ To ensure appropriate delivery, subcutaneous injections should be made at a 45° angle using a 5/8-inch, 23- to 25-gauge needle.¹¹⁶

Since syncope may occur following vaccination, vaccinees should be observed for approximately 15 minutes after the vaccine dose is administered.¹¹⁶ If syncope occurs, the patient should be observed until symptoms resolve.¹¹⁶ Syncope after vaccination occurs most frequently in adolescents and young adults.¹¹⁶

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.¹¹⁶ Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.¹¹⁶

Dosage

The usual dose of MMR is 0.5 mL and is the same for all individuals.¹⁰⁴ When reconstituted as specified, each 0.5-mL dose of MMR contains not less than 1000 TCID₅₀ of measles virus, 12,500 TCID₅₀ of mumps virus, and 1000 TCID₅₀ of rubella virus.¹⁰⁴ The entire volume of reconstituted solution in the single-dose vial should be administered.¹⁰⁴

Infants and Children 12 Months through 12 Years of Age

For primary immunization against mumps in infants and children, a 2-dose regimen of MMR is recommended and the first dose generally is administered at 12 through 15 months of age.^{102 116 162 163} For routine childhood immunization, the ACIP, AAP, and AAFP recommend that the first dose of MMR be given at 12 through 15 months of age and the second dose be routinely given at 4 through 6 years of age (just prior to entry into kindergarten or first grade).^{102 162 163} The second dose may be given earlier during any routine visit, provided at least 4 weeks (i.e., at least 28 days) have elapsed since the first dose and both the first and second doses are administered beginning at or after 12 months of age.^{162 163}

Children who received a dose of monovalent mumps virus vaccine live (no longer commercially available in the US) or MMR before 12 months of age should be considered susceptible to mumps and should be revaccinated with a 2-dose MMR regimen beginning as soon as possible after they reach their first birthday.¹⁶²

During a mumps outbreak, a dose of MMR should be considered for children 1–4 years of age who have only received 1 dose of a mumps virus-containing vaccine.¹⁷¹

Adolescents 13 through 18 Years of Age

For primary immunization against mumps in previously unvaccinated adolescents 13 through 18 years of age, a 2-dose regimen of MMR is recommended.^{102 163 171} The second dose should be administered at least 4 weeks (i.e., at least 28 days) after the initial dose.^{163 171}

Adults

For adults 19 years of age and older, primary immunization consists of 1 or 2 doses of MMR.^{102 162 169} The minimum interval between doses is 4 weeks (i.e., at least 28 days).^{116 162 169}

During a mumps outbreak, a dose of MMR should be considered for adults who have only received 1 dose of a mumps virus-containing vaccine.¹⁷¹

Cautions for Mumps Virus Vaccine Live

Systemic Effects

Subclinical Vaccine Virus Infection

The most common systemic effects associated with administration of monovalent mumps virus vaccine live (no longer commercially available in the US) have been low-grade fever and episodes of parotitis.¹⁴² However, in field trials with the vaccine prior to licensure, these and other effects did not occur more frequently in vaccinees compared with unvaccinated controls.^{142 143} Mild fever occurs occasionally; fever exceeding 39.4°C is uncommon.

Subclinical infection induced by monovalent mumps virus vaccine live has not been shown to be contagious. Rarely, parotitis or orchitis has been reported in vaccinees; however, a causal relationship to the vaccine has not been definitely established and, in most instances, these effects were probably caused by natural mumps infection. Mild lymphadenopathy, cough, and rhinitis also have been reported.¹¹⁰

Encephalitis and Aseptic Meningitis

Although a causal relationship was not definitely established, meningoencephalitis caused by mumps virus has been reported in a few children about 2.5 weeks after they received the fixed-combination vaccine containing measles, mumps, and rubella virus vaccines live (MMR; M-M-R II).^{117 118 142} The reported occurrence of encephalitis within 30 days of mumps vaccination (0.4 per million doses) does not exceed the observed background incidence of CNS dysfunction in the normal population.¹⁴²

Aseptic meningitis has been associated epidemiologically with receipt of mumps virus vaccine live containing the Urabe strain of the virus but not with formulations currently available in the US, which contains the Jeryl Lynn strain.^{110 142 144 145 162} During 1988–1992, 15 sentinel surveillance laboratories in the United Kingdom (UK) identified 13 cases of aseptic meningitis that had occurred within 15–35 days after vaccination with the Urabe strain of the virus (91 cases per million doses distributed).^{142 145 162} However, no additional cases of mumps vaccine-associated meningitis have been reported in the UK since 1992, when only mumps virus vaccine live formulated with the Jeryl Lynn strain has been used.^{142 146 162}

Other Nervous System Effects

CNS reactions, including febrile seizures, unilateral nerve deafness, and visual disturbances, have been reported very rarely within 30 days after administration of mumps virus vaccine live; however, no deaths have been reported among patients with such reactions, and almost all have fully recovered. A causal relationship between CNS reactions and the vaccine has not been definitely established, and CNS reactions do not appear to occur any more frequently in individuals receiving a mumps-containing vaccine than in the normal background population used in calculating incidence risk. In addition, there is no evidence that febrile seizures associated with mumps vaccination result in any residual seizure disorder.^{142 144}

Although sensorineural deafness has been reported rarely following mumps vaccination, data are inadequate to distinguish between vaccine and nonvaccine causation.¹⁴² Forms of optic neuritis, including retrobulbar neuritis, papillitis, and retinitis, occur rarely following viral infections, and have been reported following administration of some live virus vaccines.^{104 110}

There have been isolated cases of Guillain-Barré following administration of vaccines containing mumps virus live;¹⁶² however, the National Academy of Sciences Institute of Medicine concluded that evidence is insufficient to accept or reject a causal relationship.¹⁶²

Sensitivity Reactions

Allergic reactions such as rash, urticaria, and pruritus have occurred rarely in vaccinees, but usually are mild and of brief duration.¹⁷⁴ More serious hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions as well as related phenomena such as angioneurotic edema (including peripheral or facial edema) and bronchial spasm, have been reported rarely following administration of mumps virus vaccine live or MMR in individuals with or without an allergic history.^{104 110} Most hypersensitivity reactions have been minor, consisting of a wheal and flare or urticaria at the injection site.^{142 162} Immediate, anaphylactic reactions to mumps virus vaccine live or MMR are extremely rare.^{142 162} Although more than 70 million doses of mumps virus-containing vaccines (MMR) have been distributed in the US since the Vaccine Adverse Events Reporting System (VAERS) was implemented in 1990, only 33 cases of anaphylactic reactions have been reported after MMR vaccination.¹⁴² In addition, only 11 of these cases occurred immediately after vaccination with manifestations consistent with anaphylaxis.¹⁴²

MMR contains hydrolyzed gelatin as a stabilizer, which rarely may stimulate hypersensitivity reactions is some individuals.^{142 147 148 162} An anaphylactic reaction following MMR vaccination has been reported in the US in at least one individual with IgE-mediated anaphylactic sensitivity to gelatin,^{142 147} and similar cases have been reported elsewhere.^{142 148 162} (See Gelatin Allergy under Cautions: Sensitivity Reactions, in Precautions and Contraindications.) Erythema multiforme and Stevens-Johnson syndrome have been reported rarely with mumps virus vaccine live.¹¹⁰

Hematologic Effects

Surveillance of adverse effects in the US and elsewhere indicates that mumps virus-containing vaccines (e.g., MMR) rarely can cause clinically evident thrombocytopenia (e.g., purpura) within 2 months after vaccination.^{118 142 146 149 150 151 152 153 154}

Endocrine Effects

Natural mumps virus infection can precipitate the onset of diabetes mellitus.¹⁶² However, an association between vaccination with mumps virus vaccine live or MMR and pancreatic toxicity or subsequent development of diabetes mellitus has not been established.^{142 162}

Other Adverse Systemic Effects

Syncope, vasculitis, and pancreatitis have been reported in patients receiving mumps virus vaccine live.¹¹⁰ Diarrhea also has been reported.¹¹⁰

Local Effects

Local reactions, including soreness, burning, and stinging, may occur at the site of injection following administration of mumps virus vaccine live. These local reactions are usually of short duration and may occur because of the slightly acidic pH of the vaccine. Purpura and allergic reactions (e.g., wheal and flare) at the injection site have been reported very rarely.¹¹⁰

Precautions and Contraindications

MMR is contraindicated in individuals who are hypersensitive to the vaccine or any component in the formulation, including gelatin.¹⁰⁴ (See Gelatin Allergy under Cautions: Sensitivity Reactions, in Precautions and Contraindications.) In addition, MMR is contraindicated in those with a history of anaphylactic or anaphylactoid reaction to neomycin.¹⁰⁴ (See Neomycin Allergy under Cautions: Sensitivity Reactions, in Precautions and Contraindications.)

MMR is contraindicated in certain other individuals.¹⁰⁴ (See Individuals with Altered Immunocompetence under Cautions: Precautions and Contraindications and Cautions: Pregnancy, Fertility, and Lactation.)

Sensitivity Reactions

Prior to administration, the recipient and/or parent or guardian should be questioned concerning reactions to previous doses of mumps virus-containing vaccine or MMR.^{104 110}

Epinephrine should be available for immediate treatment of an anaphylactic reaction if such a reaction occurs.¹⁰⁴

Allergy to Egg-related Antigens

MMR is produced in chick embryo cell culture;¹⁰⁴ individuals with a history of anaphylactic, anaphylactoid, or other immediate reaction (e.g., urticaria, swelling of the mouth and throat, difficulty in breathing, hypotension, shock) following ingestion of eggs may be at increased risk of immediate-type hypersensitivity reactions after receiving vaccines containing traces of chick embryo antigen.^{104 168} The manufacturer states that the benefits and risks should be carefully evaluated before considering vaccination in individuals with a history of immediate-type hypersensitivity following ingestion of eggs and such individuals should be vaccinated with extreme caution and with adequate treatment on hand should a reaction occur.¹⁰⁴

The US Public Health Service Advisory Committee on Immunization Practices (ACIP) and others previously recommended that, since mumps virus vaccine live is produced in chick embryo fibroblasts, vaccination with mumps virus vaccine live in individuals with a history of anaphylactoid reactions to egg ingestion be deferred until after appropriate skin testing and desensitization procedures had been performed and that the vaccine be administered only with extreme caution (in a setting where an immediate allergic reaction can be detected and treated).¹⁰⁰ However, the predictive value and necessity of such testing have been questioned by most experts since mumps virus vaccine live has been administered safely to some children with histories of immediate reactions to eggs and most anaphylactic reactions to the vaccine are not associated with egg allergy but with other vaccine components.^{102 116 131 132 133 135 142 162} Therefore, ACIP states that skin testing and use of special protocols are not required when administering a mumps virus-containing vaccine in individuals with a history of anaphylactic-like reactions after egg ingestion.^{102 116 142 162} In addition, skin testing unnecessarily delays administration of the vaccine.^{131 132 133 162} A reasonable precaution for individuals with a history of immediate reactions to eggs is to administer MMR in a supervised setting where appropriate emergency treatment material is available.^{131 132 133 135}

Evidence indicates that individuals are not at increased risk of hypersensitivity reactions to MMR if they have egg allergies that are not anaphylactic or anaphylactoid in nature and administration of the vaccine to these individuals should follow the usually recommendations.¹⁰⁴ (See Uses.) There is no evidence that individuals with allergies to chickens or feathers are at increased risk of allergic reactions to the vaccine.¹⁰⁴

Neomycin Allergy

Because MMR contains trace amounts of neomycin, the vaccine is contraindicated in individuals who have had an anaphylactic reaction to topically or systemically administered neomycin.¹⁰⁴

Neomycin allergy usually is characterized by a delayed-type (cell-mediated) hypersensitivity reaction, such as contact dermatitis, rather than an anaphylactic reaction.^{104 116} Following administration of mumps virus vaccine live to individuals who have had a delayed-type hypersensitivity reaction to neomycin, the typical adverse reaction, if any, is a contact dermatitis (e.g., characterized by an erythematous, pruritic nodule or papule) occurring within 48–96 hours.^{110 142 162}

The ACIP and the American Academy of Pediatrics (AAP) state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type hypersensitivity reaction to neomycin if benefits of vaccination outweigh risks.^{116 142 162}

Gelatin Allergy

The possibility of allergic reactions to hydrolyzed gelatin, which is present in MMR as a stabilizer, should be considered since anaphylactic reactions to the vaccine have been reported rarely in individuals with anaphylactic sensitivity to gelatin.^{102 104 116 142 162} MMR should not be administered to individuals with a history of anaphylactic reactions to gelatin or gelatin-containing products.¹⁰² Although skin testing for gelatin sensitivity before administering the vaccine to such individuals can be considered, there are no specific protocols for this purpose.¹¹⁶ Because gelatin used in vaccines manufactured in the US usually is derived from porcine sources and because 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.¹⁶²

Individuals with Altered Immunocompetence

MMR generally is contraindicated in individuals with primary immunodeficiencies (e.g., cellular immune deficiency, hypogammaglobulinemia, dysgammaglobulinemia) and in individuals with suppressed immune responses resulting from acquired immunodeficiency syndrome (AIDS) or other clinical manifestations of human immunodeficiency virus (HIV) infection, blood dyscrasias, leukemia, lymphomas of any type, or any other malignant neoplasms affecting the bone marrow or lymphatic systems.¹⁰⁴

Because replication of mumps vaccine virus may be potentiated in individuals with primary immunodeficiencies (e.g., cellular immune deficiency, hypogammaglobulinemia, dysgammaglobulinemia) or with suppressed immune response resulting from leukemia, lymphoma, other malignancies affecting the bone marrow or lymphatic system, or blood dyscrasias, concern exists about the potential risk of administering any live virus vaccine to such individuals.^{119 142 162} Severe immunosuppression may be caused by many disease conditions (e.g., congenital immunodeficiency, HIV infection, hematologic or generalized malignancy) and by immunosuppressive therapy.¹⁶² For some conditions, all infected individuals are severely immunocompromised, whereas for other conditions, the degree of immune compromise depends on the severity of the condition, which in turn depends on the disease and treatment stage.¹⁶² Although there is no evidence that mumps virus-containing vaccine causes serious illness in immunocompromised individuals, concern exists about the potential risk of administering any live vaccine to such individuals.¹⁶² Therefore, with the exception of individuals with HIV infection, immunocompromised individuals should not receive a mumps virus-containing vaccine,^{119 127 142} especially those who are severely immunosuppressed.¹⁶² Ultimately, the patient’s clinician must assume responsibility for determining whether the patient is severely immunocompromised based on clinical and laboratory assessment.¹⁶² MMR should not be given to an individual with a family history of congenital or hereditary immunodeficiency until the immunocompetence of the individual has been documented.¹⁰⁴ Because mumps vaccinees do not transmit mumps vaccine virus, the risk of mumps exposure in such immunocompromised individuals may be reduced by vaccinating their close susceptible contacts against mumps.¹⁴² The greatest risk associated with administering a live mumps virus-containing vaccine in immunosuppressed patients appears to be with vaccines that also include live measles virus as a component.¹⁶²

MMR generally is contraindicated in individuals receiving immunosuppressive therapy (e.g., corticotropin, corticosteroids [at immunosuppressive dosages], alkylating agents, antimetabolites, radiation therapy),¹⁶² although the manufacturer states that the vaccine is not contraindicated in individuals receiving corticosteroids as replacement therapy (e.g., for Addison’s disease).¹⁰⁴ (See Drug Interactions: Immunosuppressive Agents.)

The ACIP states that use of live virus vaccines can be considered in patients with leukemia, lymphoma, or other malignancies if the disease is in remission and chemotherapy was terminated at least 3 months prior to vaccination.¹¹⁶

Antibody responses to MMR and efficacy may be decreased in immunocompromised individuals.¹⁰⁴

HIV-infected Individuals

The ACIP, AAP, US Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society, and others state that MMR should be administered to all asymptomatic HIV-infected individuals according to the usually recommended immunization schedules and should be considered for all symptomatic HIV-infected individuals who do not have evidence of severe immunosuppression and who otherwise would be eligible for such vaccination.^{102 127 142 162 164 182} The presence of immunocompromised or HIV-infected individuals in a household does not preclude administration of MMR to other household members.^{102 162}

MMR is contraindicated in HIV-infected individuals with severe immunosuppression.^{102 127 142 162 164 182} (See HIV-Infected Individuals under Uses: Primary Immunization.)

Fever

Following vaccination, patients should be monitored for temperature elevations.^{104 109}

Risk of Transmissible Agents in Preparations Containing Albumin

MMR contains recombinant human albumin.¹⁰⁴

Monovalent mumps virus vaccine live (no longer commercially available in the US) and the fixed-combination vaccine containing measles, mumps, rubella, and varicella antigens (MMRV; ProQuad) contain albumin human.^{110 168} Since albumin human is prepared from pooled human plasma, it is a potential vehicle for transmission of human viruses, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD).¹¹⁰

Concomitant Illness

The decision whether to administer or delay administration of MMR in an individual with a current or recent acute illness depends largely on the severity of symptoms and etiology of the illness.^{116 139 140 141 162} The manufacturer states that MMR is contraindicated in patients with any febrile respiratory illness or other active febrile infections.¹⁰⁴ The ACIP and AAP state that minor acute illness, such as diarrhea or mild upper respiratory infection (with or without fever), does not preclude vaccination.^{102 116 139 140 141 162} However, vaccination of individuals with moderate or severe acute illness (with or without fever) generally should be deferred until they have recovered from the acute phase of the illness.^{116 162} This precaution avoids superimposing adverse effects of the vaccine on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccination.¹¹⁶ However, data generally are not available on the safety and immunogenicity of measles, mumps, and rubella virus-containing vaccines in individuals with moderate or severe febrile illness.¹⁶²

Thrombocytopenia

Individuals with a history of thrombocytopenic purpura or thrombocytopenia may be at increased risk of developing clinically apparent thrombocytopenia after vaccination.¹⁰⁴ Thrombocytopenia has worsened in those with preexisting thrombocytopenia and may worsen with subsequent doses.¹⁰⁴ Serologic evidence of immunity may be obtained in lieu of vaccination.¹⁰⁴ The decision to vaccinate such individuals should depend on the benefits of immunity and the risks of recurrence or exacerbation of thrombocytopenia after vaccination or during natural infection with viruses.¹⁰⁴

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),^{176 177} evidence has been insufficient to support an association between neurodevelopmental disorders and MMR.^{176 177 178} 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.¹⁷⁷

Tuberculosis

Vaccination is not recommended for individuals with untreated, active tuberculosis.¹⁰⁴ Defer vaccination in these individuals until antituberculosis therapy has been initiated.^{102 104 116} Administration of live, attenuated vaccines is not contraindicated in individuals with a positive tuberculin skin test who do not have active tuberculosis infection.¹¹⁶ Tuberculin testing is not a prerequisite for administration of mumps virus vaccine live or MMR.^{102 162}

Transmission of Vaccine Virus

MMR contains live, attenuated virus;¹⁰⁴ there is a theoretical risk that transmission of vaccine virus could occur between vaccinees and susceptible contacts.¹⁰⁴

Transmission of live, attenuated mumps from vaccinees to susceptible contacts has not been reported.¹¹⁰

Limitations of Vaccine Effectiveness

MMR may not protect all individuals from mumps.¹⁰⁴

Safety and efficacy of MMR have not been established for postexposure prophylaxis following exposure to mumps.¹⁰⁴ (See Uses: Postexposure Vaccination.)

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.¹⁰⁴

MMR that has been mishandled or has not been stored at the recommended temperature should not be administered.¹⁷² (See Chemistry and Stability: Stability.)

Lyophilized and reconstituted vaccine should be protected from light at all times because exposure to light may inactivate the vaccine virus.^{104 172}

Freezing or exposing the diluent supplied by the manufacturer to freezing temperatures should be avoided;¹⁷² the diluent may be refrigerated or stored at room temperature.^{104 172}

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.¹⁷²

Pediatric Precautions

Safety and efficacy of MMR in children younger than 6 months of age have not been established, and use of the vaccine in this age group is not recommended.¹⁰⁴

Geriatric Precautions

Clinical studies of MMR did not include sufficient numbers of seronegative individuals 65 years of age or older to determine whether these individuals respond differently than younger individuals.¹⁰⁴ Other reported clinical experience has not identified differences in responses between geriatric and younger individuals.¹⁰⁴

Mutagenicity and Carcinogenicity

The mutagenic or carcinogenic potential of MMR have not been evaluated.¹⁰⁴

Pregnancy, Fertility, and Lactation

Pregnancy

The effect of MMR on fetal development is not known.¹⁰⁴ Mumps virus vaccine live has been shown to distribute into the placenta^{102 110 142 155} and fetus,¹⁴² but there is no evidence that vaccines containing mumps virus can cause congenital malformations in humans.^{102 110 142} Because of the theoretical risk of harm to the fetus, the ACIP and AAP state that it is prudent to avoid administering mumps virus-containing vaccine to pregnant women.^{102 116 142 162} Although the manufacturer states that MMR should not be administered to pregnant women and that appropriate steps be taken to prevent conception for 3 months following vaccination,¹⁰⁴ the ACIP and AAP state that women who receive MMR should avoid becoming pregnant for 4 weeks (i.e., 28 days) after vaccination.^{102 142 162 174}

Lactation

It is not known whether MMR is distributed into milk.¹⁰⁴ The manufacturer states that MMR should be administered with caution to nursing women.¹⁰⁴ The ACIP states that breastfeeding generally is not a contraindication to administration of mumps virus-containing vaccine since live vaccines appear to pose no special problems for the mother or her nursing infant.^{116 162}

Drug Interactions

Blood Products

Blood products (e.g., whole blood, packed red blood cells, plasma) may interfere with the immune response to certain live virus vaccines, including measles, mumps, and rubella virus vaccine live (MMR; M-M-R II); therefore, MMR should not be administered simultaneously with or for specified intervals before or after administration of blood products.^{102 116 162}

Administration of MMR should be deferred for at least 3 months following administration of red blood cells (with adenine-saline added); for at least 6 months following administration of packed red blood cells or whole blood; and for at least 7 months following administration of plasma or platelet products.¹¹⁶

After receiving MMR, vaccinees should avoid blood products for 2 weeks; if use of a blood product is considered necessary during this period, a repeat vaccine dose should be given after the recommended interval unless serologic testing is feasible and indicates a response to the vaccine was attained.¹¹⁶

Immunosuppressive Agents

Individuals receiving immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticotropin, corticosteroids [at immunosuppressive dosages], radiation therapy) may have a diminished response to mumps virus-containing vaccine and replication of the virus may be potentiated. Vaccination with MMR should be deferred until the immunosuppressive agent is discontinued; the manufacturer states that individuals receiving corticosteroids as replacement therapy (e.g., those with Addison’s disease) generally may receive the vaccine.¹⁰⁴ The exact interval between discontinuance of immunosuppressive therapy and regaining the ability to respond to live virus vaccines is not known, but live viral vaccines generally should not be administered for at least 3 months after discontinuance of immunosuppressive therapy.^{127 142 162} Individuals with leukemia in remission who have not received chemotherapy for at least 3 months may receive a live virus vaccine.^{102 116 119 142 162} The precise amount and duration of systemically absorbed corticosteroid therapy needed to suppress the immune system of an otherwise healthy individual are not well defined.^{127 142 162} Although of recent theoretical concern, there is no evidence of increased severe reactions to live vaccines in individuals receiving corticosteroid aerosol therapy, and such therapy is not in itself a reason to delay vaccination.¹⁴² Most experts, including the US Public Health Service Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics (AAP), agree that short-term (less than 2 weeks), low- to moderate-dose systemic corticosteroid therapy; long-term, alternate-day, systemic corticosteroid therapy using low to moderate doses of short-acting drugs; topical corticosteroid therapy (e.g., nasal, cutaneous, ophthalmic); aerosol corticosteroid therapy; or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive in usual dosages and do not necessarily contraindicate vaccination with live virus vaccines.^{102 116} Although the immunosuppressive effects of corticosteroid therapy vary, many clinicians consider a dose equivalent to 2 mg/kg or 20 mg total of prednisone daily for 2 weeks or longer as sufficiently immunosuppressive to raise concerns about the safety of vaccination with live virus vaccines.^{127 142 162}

Immune Globulins

Antibodies contained in immune globulin preparations (e.g., immune globulin IM [IGIM], immune globulin IV [IGIV], hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella-zoster immune globulin [VZIG]) may interfere with the immune response to certain live virus vaccines, including mumps virus-containing vaccine.¹¹⁶ The manufacturer, ACIP, and AAP state that, since passively acquired antibody may interfere with the response to live attenuated virus vaccines, administration of MMR should be given at least 2 weeks before or deferred for at least 3 months after administration of an immune globulin.^{100 102 104 116 142 174} The effect of immune globulin on the response to MMR has not been fully determined.^{116 142} The ACIP states that if simultaneous administration of an immune globulin preparation and mumps virus-containing vaccine becomes necessary because of imminent exposure to disease, vaccine-induced immunity may be compromised.¹¹⁶ If simultaneous vaccination is deemed necessary, the live virus vaccine should be administered at a separate site remote from that of the immune globulin and, unless there is serologic evidence of an adequate antibody response to the live virus vaccine, an additional dose of vaccine should be administered 3 months later.¹¹⁶ If a vaccine containing mumps in combination with measles virus vaccine live (MMR) is used, a longer interval (up to at least 11 months) may be required to ensure an adequate immune response to the vaccine.^{116 142} (See Drug Interactions: Immune Globulins, in Measles Virus Vaccine Live 80:12.) In addition, an immune globulin should not be administered until at least 2 weeks after vaccination if possible.^{100 116} If an immune globulin must be administered within 14 days after administration of a mumps virus-containing vaccine, an additional dose of the vaccine should be given 3 months after the immune globulin unless serologic testing, indicates that an adequate antibody response to the vaccine occurred; an additional dose of the vaccine is generally unnecessary if the interval between vaccination and administration of the immune globulin is longer than 14 days.^{100 116}

Live Vaccines

Measles, Mumps, Rubella, and Varicella Vaccines

Mumps virus vaccine live may be administered concurrently with rubella virus vaccine live, measles virus vaccine live, and varicella virus vaccine live.¹¹⁶

Mumps virus vaccine live is commercially available in a fixed-combination vaccine containing measles virus vaccine live and rubella virus vaccine live (MMR) to facilitate concomitant administration of all 3 antigens.¹⁰⁴ Administration of MMR results in immunologic responses similar to those obtained with concurrent administration of the 3 antigens at separate sites.¹¹⁶

MMR may be administered concurrently with monovalent varicella virus vaccine live (Varivax) at a different site using a separate syringe.^{102 104 106 116 183} Results of studies in healthy children 12–36 months of age indicate that seroconversion rates, antibody responses, and adverse effects reported with simultaneous administration of the vaccines are similar to those reported when the vaccines are administered 6 weeks apart.¹⁸³ Because there is a theoretical concern that the immune response to one live viral vaccine may be impaired if administered within 1 month of another, if MMR and varicella virus vaccine live are not administered simultaneously then they should be administered at least 1 month apart.^{102 106 116} There is some evidence that administration of varicella virus vaccine live less than 30 days after MMR decreases the effectiveness of the varicella vaccine.¹⁰⁶ Results of a retrospective cohort study that used data from the Vaccine Safety Datalink (VSD) project and included children 12 months of age or older who were vaccinated during January 1995 to December 1999 indicate that administration of varicella virus vaccine live less than 30 days after MMR results in a 2.5-fold increase in the incidence of breakthrough varicella infections.^{106 116} However, when the vaccines were administered concurrently, there was no increase in the risk for breakthrough infections.¹⁰⁶

Mumps virus vaccine live also is commercially available in a fixed-combination vaccine containing MMR and varicella virus vaccine live (MMRV; ProQuad).¹⁶⁸ This fixed-combination vaccine is safe and effective in healthy children 12 months through 12 years of age.¹⁶⁸ Studies using MMRV (ProQuad) in healthy children 1–6 years of age indicate that the antibody responses against measles, mumps, rubella, and varicella antigens following a single dose of ProQuad are similar to those obtained after a single dose of MMR and a single dose of varicella virus vaccine live (Varivax).¹⁶⁸ However, there is some evidence that the relative risk for febrile seizures in infants may be higher with the fixed-combination vaccine MMRV than that reported when a dose of single-antigen varicella virus vaccine live (Varivax) and a dose of MMR are given concomitantly.¹⁶⁸

Influenza Vaccine Live Intranasal

Because of theoretical concerns that the immune response to one live virus vaccine might be impaired if given within 30 days of another live virus vaccine, if MMR and influenza virus vaccine live intranasal are not administered on the same day, they should be administered at least 4 weeks apart.¹¹⁶

Other Live Vaccines

Some oral live vaccines (e.g., rotavirus vaccine live oral, typhoid vaccine live oral) can be administered concomitantly with or at any interval before or after MMR.¹¹⁶

Because of theoretical concerns that the immune response to other live virus vaccines might be impaired if given within 30 days of another live virus vaccine, if MMR and yellow fever vaccine are not administered on the same day, they should be administered at least 4 weeks apart.¹¹⁶

Inactivated Vaccines and Toxoids

MMR may be administered concurrently with (using different syringes and different injection sites) or at any interval before or after inactivated vaccines, recombinant vaccines, polysaccharide vaccines, or toxoids.¹¹⁶

MMR may be given concurrently with Haemophilus influenzae type b (Hib) conjugate vaccines at a different site using a separate syringe.^{100 104 125 126}

Although specific studies evaluating simultaneous administration of MMR and hepatitis A vaccine, hepatitis B vaccine, diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP) or tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) are not available, these vaccines may be administered concomitantly.^{100 102 105 120 121 122 123 124}

MMR may be given concomitantly with parenteral inactivated influenza vaccines (using different syringes and different injection sites) or at any interval before or after administration of inactivated influenza vaccines.¹¹⁶

MMR may be administered concurrently with pneumococcal vaccine, including pneumococcal conjugate vaccine (PCV) or pneumococcal 23-valent polysaccharide vaccine (PPSV23), at a different site using a separate syringe.^{116 166 167}

Laboratory Test Interferences

Tuberculin

Live attenuated measles, mumps, and rubella virus vaccines have been reported to temporarily suppress tuberculin skin sensitivity; therefore, tuberculin skin tests (if required) should be done before, simultaneously with, or at least 4–6 weeks or longer after administration of measles, mumps, and rubella virus vaccine live (MMR; M-M-R II).^{110 162}

Pharmacology

Monovalent mumps virus vaccine live (no longer commercially available in the US) and the fixed-combination vaccine containing measles, mumps, and rubella antigens (measles, mumps, and rubella virus vaccine live [MMR; M-M-R II]) stimulate active immunity to mumps by inducing production of specific antibodies.^{104 110} Studies using monovalent mumps virus vaccine live indicate that a single subcutaneous dose produces a serologic response in about 97% of susceptible children older than 12 months of age and about 93% of susceptible adults; however, a small percentage (1–5%) of vaccinees may fail to seroconvert after the primary dose.¹¹⁰ Studies in the US have reported that 1 dose of mumps virus vaccine live was 78–91% effective in preventing clinical mumps with parotitis. Although vaccine-induced antibody titers are generally lower than those stimulated by natural mumps infection,^{110 162} observations from 30 years of use of the live vaccine indicate the persistence of antibody and continuing protection against infection.¹⁶² The duration of immunity following administration of mumps virus-containing vaccine is believed to be greater than 25 years, and is probably lifelong in most vaccine recipients.¹⁷⁴ Clinical efficacy of the vaccine reportedly ranges from 75–95%.^{102 162 174} The killed mumps virus vaccine (available in the US from 1950 through 1978) induced antibody, but the resulting immunity was transient.

Chemistry and Stability

Chemistry

Mumps virus vaccine live is a preparation of live, attenuated organisms of the Jeryl Lynn (B level) strain of mumps virus.¹¹⁰ Monovalent mumps virus vaccine live (Mumpsvax) is no longer commercially available in the US.¹⁷⁹ Mumps virus vaccine live is commercially available in the US in a fixed-combination vaccine with measles virus vaccine live and rubella virus vaccine live (MMR; M-M-R II)¹⁰⁴ and in a fixed-combination vaccine containing MMR and varicella virus vaccine live (MMRV; ProQuad).¹⁶⁸

Vaccines containing mumps virus vaccine live meet standards established by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. The mumps virus used in production of these vaccines is propagated and attenuated by serial passage in chick embryo tissue culture.¹¹⁰ The potency of MMR is expressed in terms of the amount of virus estimated to infect 50% of a number of standardized tissue culture preparations under specified conditions (tissue culture infective dose 50% or TCID₅₀). Following reconstitution with the diluent provided by the manufacturer, each 0.5-mL dose of reconstituted MMR contains not less than 1000 TCID₅₀ of measles virus, 12,500 TCID₅₀ of mumps virus, and 1000 TCID₅₀ of rubella virus.¹⁰⁴ Each 0.5-mL dose of MMR also contains sorbitol (14.5 mg), sodium phosphate, sucrose (1.9 mg), sodium chloride, hydrolyzed gelatin (14.5 mg), recombinant albumin human (up to 0.3 mg), fetal bovine serum (less than 1 part per million), and approximately 25 mcg of neomycin.¹⁰⁴ The cells, virus pools, fetal bovine serum, and albumin human used in preparation of MMR are screened for the absence of adventitious agents; the albumin human is processed using the Cohn cold alcohol fractionation procedure.¹⁰⁴

Lyophilized MMR occurs as light yellow compact crystalline plugs and the reconstituted vaccine occurs as a clear yellow solution.^{104 110} MMR does not contain thimerosal or any other preservative.¹⁰⁴

Stability

In lyophilized form, MMR should be refrigerated at 2–8°C but may be frozen.¹⁰⁴ The vials containing diluent provided by the manufacturer may be stored in the refrigerator at 2–8°C or at room temperature.¹⁰⁴ During shipping, MMR must be stored at 10°C or less¹¹⁰ and may be packed in solid carbon dioxide (dry ice).¹⁷² If the vaccine is shipped with dry ice, the diluent must be shipped separately.¹⁷²

Following reconstitution with the diluent provided by the manufacturer, MMR should be refrigerated at 2–8°C and discarded if not used within 8 hours.^{104 172} Both the lyophilized and reconstituted vaccine should be protected from light, which may inactivate the virus.^{104 172}

Preparations

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

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

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