Professional Drug Information > M-R-VAX II

Measles and Rubella Virus Vaccine Live (Systemic)

VA CLASSIFICATION
Primary: IM100


Note: This monograph is specific for the sterile lyophilized preparation of a more attenuated line of measles virus, derived from Enders" attenuated Edmonston strain and grown in cell cultures of chick embryos, and the Wistar RA 27/3 strain of live attenuated rubella virus grown in human diploid cell (WI-38) culture ^{01}.

Commonly used brand name(s): M-R-VAX II.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

^†Not commercially available in Canada.

Category:


Immunizing agent (active)—

Indications

General considerations
Persons generally can ^{53} be considered immune to measles and/or rubella only if they have documentation of adequate ^{53} immunization with measles and/or rubella vaccines on or after their first birthdays, if they have laboratory evidence of measles and/or rubella immunity, or if they have a physician's diagnosis of previous measles infection. Since the clinical diagnosis of rubella infection is unreliable, it should not be considered in assessing immune status to rubella ^{{01} {02} {03} {04}}.

Most individuals born before 1957 can generally be considered immune to measles and mumps because of probable previous infection, even though, in the case of mumps, they may not have had clinically recognizable disease ^{{01} {02} {03} {04}}. However, birth before 1957 provides only presumptive evidence of immunity; measles can occur in some persons born before 1957 ^{53}.

Although serologic tests may be conducted to determine the susceptibility of persons of unknown immunity, studies have indicated there is no evidence of increased risk of adverse reactions due to vaccination with live measles and/or rubella vaccine virus in persons already immune to measles and/or rubella ^{53}.

Previously nonimmunized children of susceptible pregnant women should receive live attenuated rubella vaccine because an immunized child is less likely to acquire natural rubella and introduce the virus into the household ^{{01} {03} {04}}.

Monovalent measles vaccine should be used to immunize infants 6 to 12 months of age during measles epidemics ^{52}, although combined measles, mumps, and rubella or measles and rubella vaccines can be used if monovalent measles vaccine is not available ^{53}.

Measles, mumps, and rubella virus vaccine live should be used for vaccinating individuals who are likely to be susceptible to more than one of these viruses, unless otherwise contraindicated ^{03}.

Vaccines containing measles antigen should be administered routinely to persons 12 to 15 months of age or older under routine conditions ^{46}.

Accepted

Measles and rubella (prophylaxis)—Measles and rubella virus vaccine live is indicated for simultaneous immunization against measles (rubeola; morbilli; coughing, hard, red, or 10-day measles) and rubella (German measles) ^{07} in persons 12 to 15 months of age or older ^{01} who already have evidence of immunity to mumps ^{53}.
—The main objectives of measles immunization are to prevent transmission of measles virus and ^{53} to prevent severe complications, such as pneumonia, ear infections, sinusitis, encephalitis, subacute sclerosing panencephalitis, gastroenteritis ^{48}, and death, which may arise from a measles infection ^{33}. The risk of serious complications and death from a natural measles infection is greater for adults and infants than for children and adolescents.
—The main objective of rubella immunization is to prevent intrauterine infection of the fetuses of women exposed to rubella, which can result in miscarriage, abortion, stillbirth, or in congenital rubella syndrome in the neonate. ^{{01} {03} {04}}
—Unless otherwise contraindicated, all susceptible persons 12 months of age or older ^{{05} {46}} should be immunized against measles and rubella, including:

   • Women of childbearing potential ^{{01} {03} {13} {15} {38} {40}}, if they are not pregnant and if they are counseled not to become pregnant for 3 months following vaccination. Since there is an increased risk of acquiring rubella while traveling outside the U.S., women of childbearing age should be immunized before leaving the country ^{{01} {03} {04}}.
   • Postpartum women, preferably before discharge from the hospital. Breast-feeding is not a contraindication to vaccination. Although rubella vaccine virus can be distributed into breast milk, breast-fed newborns generally remain asymptomatic ^{53}.
   • Persons traveling outside the U.S. These persons should receive measles and rubella virus vaccine live prior to international travel ^{{01} {34}}.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Measles and rubella virus vaccine live contains a sterile lyophilized preparation of a more attenuated line of measles virus, derived from Enders' attenuated Edmonston strain and grown in cell cultures of chick embryos, and the Wistar RA 27/3 strain of live attenuated rubella virus grown in human diploid cell (WI-38) culture. ^{01} The vaccine viruses are the same as those used in the manufacture of measles virus vaccine live, and rubella virus vaccine live. The two viruses are mixed before they are lyophilized ^{01}.

Mechanism of action/Effect:

Following subcutaneous injection, measles and rubella virus vaccine live produces a modified, noncommunicable measles and rubella infection and provides active immunity to measles and rubella ^{{01} {15}}.


Protective effect

Clinical studies of 237 double seronegative children, 10 months to 10 years of age, demonstrated that measles and rubella virus vaccine live is highly immunogenic and generally well tolerated. In these studies, a single injection of measles and rubella virus vaccine live induced measles hemagglutinin-inhibition (HI) antibodies in 95%, and rubella HI antibodies in 99%, of susceptible individuals ^{01}. The presence of these antibodies has been correlated with clinical protection and their absence considered indicative of susceptibility ^{32}.

The RA 27/3 rubella strain in measles and rubella virus vaccine live elicits higher immediate postvaccination HI, complement-fixing, and neutralizing antibody levels than other strains of rubella vaccine and has been shown to induce a broader profile of circulating antibodies, including anti-theta and anti-iota precipitating antibodies. The RA 27/3 rubella strain immunologically simulates natural infection more closely than other rubella vaccine viruses. The increased levels and broader profile of antibodies produced by the RA 27/3 strain of rubella virus vaccine appear to correlate with greater resistance to subclinical reinfection with the wild virus, and provide greater confidence for lasting immunity ^{{01} {03} {04}}.


Duration of protective effect

Vaccine-induced antibody levels following administration of measles and rubella virus vaccine live have been shown to persist for up to 11 years without substantial decline ^{01}. Protective antibodies have been observed 21 years after measles vaccination and 18 years after rubella vaccination ^{47}. Continued surveillance will be necessary to determine further duration of antibody persistence ^{{01} {25} {27}}. Continuous serosurveillance is important to monitor the immunity status in the population and especially to ensure that the immunity is sufficient during childbearing years ^{{14} {27}}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients allergic to systemic or topical neomycin may be allergic to the measles and rubella virus vaccine live because each 0.5-mL dose contains approximately 25 mcg of neomycin, which is used in the production of the vaccine to prevent bacterial overgrowth in the viral culture ^{{01} {23}}. A history of hypersensitivity reactions (such as delayed-type allergic reaction or contact dermatitis) to neomycin generally does not preclude immunization ^{{01} {23}}. Anaphylaxis due to topically or systemically administered neomycin precludes immunization ^{53}.

Patients allergic to gelatin also may be allergic to measles and rubella virus vaccine live, since gelatin is used as a stabilizer in the production of the vaccine ^{52}.

Patients allergic to eggs also may be allergic to the measles and rubella virus vaccine live, since measles virus vaccine is produced in chick embryo cell cultures ^{{17} {19}}. However, the vaccine may be administered to egg-allergic children without prior skin testing or the use of protocols requiring gradually increasing doses of vaccine ^{53}. There is no evidence to indicate that persons with allergies to chicken or chicken feathers are at increased risk of reaction to the vaccine ^{50}.

Pregnancy/Reproduction

Pregnancy—
Although adequate studies have not been done in humans, use in pregnant women is not recommended ^{{01} {23}}. Considerable complications ^{42}, including increased rates of spontaneous abortion, premature births, low-birth-weight neonates, and possibly, congenital defects, have been observed with natural measles infection during pregnancy. The possibility exists that the measles virus vaccine may cause similar effects ^{{01} {02} {03}}.

Rubella vaccine virus crosses the placenta and has been recovered from the products of conception of some aborted fetuses of women who received the vaccine just prior to or during pregnancy. However, from 1971 through 1988, the Centers for Disease Control and Prevention (CDC) monitored 210 pregnant women who had received the RA 27/3 strain of rubella virus vaccine 3 months before or after conception and who carried their pregnancies to term. Although some neonates had serologic evidence of rubella virus infection, none had malformations associated with congenital rubella syndrome ^{{01} {03} {04} {08} {41}}. Therefore, vaccination of a pregnant woman should not in itself indicate the need for abortion, although the final decision rests with the woman and her physician ^{41}. The risk of congenital rubella syndrome associated with maternal infection with the wild virus during the first trimester of pregnancy is at least 20% ^{41}. The risk of teratogenicity is not fully known; although it appears to be minimal, there is still a theoretical risk of fetal abnormality caused by the vaccine virus ^{01}.

In addition, it is recommended that pregnancy be avoided for 3 months following vaccination ^{{01} {02} {03} {04}}.

Studies have not been done in animals ^{{01} {02} {03} {04}}.

FDA Pregnancy Category C ^{{01} {02} {03} {04}}.

Breast-feeding

It is not known whether measles vaccine is distributed into breast milk. Although rubella vaccine may be distributed into breast milk and infants may subsequently show serologic evidence of rubella infection or mild clinical illness typical of acquired rubella, studies have not shown that these effects cause serious clinical problems ^{{01} {02} {03} {04} {05}}.

Pediatrics

Infants up to 15 months of age may fail to respond to the measles component of the vaccine ^{44} due to the presence of residual circulating measles antibody of maternal origin ^{{01} {16} {26} {31}}. This effect usually starts to wane after the child reaches 6 months of age ^{31}. However, children born to younger mothers might respond well to measles vaccine administered at 12 months of age ^{46}. In one study, children randomly received measles vaccine at either 12 or 15 months of age. The measles antibody response to measles, mumps, and rubella virus vaccine was 93 ^{46} to 95% ^{31} when the vaccine was administered at 12 months of age, and 98% when it was administered at 15 months of age ^{{31} {46}}. Among children of mothers born after 1961, who probably had received a measles vaccine and were less likely to have had measles infection than women born in previous years, the seroconversion rate was 96% among children vaccinated at 12 months of age, and 98% among those vaccinated at 15 months of age ^{46}. Based on these findings, the Committee on Infectious Diseases of the American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) recommend administration of the first dose of measles-containing vaccine at 12 to 15 months of age ^{46}. Both AAP and ACIP recommend that all children receive a second dose of measles-containing vaccine ^{{43} {46}}. The second dose of measles-containing vaccine (preferably administered as measles, mumps, and rubella virus vaccine live) is routinely recommended at 4 to 6 years of age or at 11 to 12 years of age, but may be administered at any visit, provided at least 1 month has elapsed since receipt of the first dose ^{{10} {39}}. Children who were vaccinated when younger than 12 months of age should be revaccinated at 12 to ^{53} 15 months of age ^{{01} {05}}, provided at least 1 month has elapsed since the previous dose of the vaccine was administered ^{53}. Children who received the monovalent measles vaccine rather than the combination measles, mumps, and rubella vaccine live on or after their first birthdays also should receive a primary dose of mumps and rubella vaccines. Doses of measles, mumps, and rubella vaccine live or other measles-containing vaccines should be separated by at least 1 month ^{05}.

If exposure to measles infection has occurred within 72 hours or is imminent, children between 6 and 15 months of age can be vaccinated, provided that those vaccinated before their first birthdays are revaccinated at 15 months of age. There is some evidence to suggest that infants immunized at younger than 12 months of age may not develop sustained antibody levels when later reimmunized. The advantage of early protection must be weighed against the chance for failure to respond adequately on reimmunization ^{{01} {02} {03}}.

It is also very important to vaccinate children infected with human immunodeficiency virus (HIV) against measles ^{51}.

Children with end-stage renal disease receiving hemodialysis have a degree of immunosuppression that reduces their response to vaccination ^{47}. Therefore, it may be necessary to monitor postvaccination antibody levels in children with end-stage renal disease, and to revaccinate those children who have failed to demonstrate seroconversion ^{47}.


Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Blood products or
Immune globulins    (concurrent administration with measles and rubella virus vaccine live may interfere with the patient's immune response to the vaccine because of the possibility of antibodies to measles and rubella viruses in these products; measles and rubella virus vaccine live should be administered at least 14 days before, or 3 to 11 ^{53} months after administration of blood products or immune globulins ^{{01} {05}}, depending on the product and dose received ^{53})


» Immunosuppressive agents or
» Radiation therapy    (because normal host defense mechanisms are suppressed, concurrent use with measles and rubella vaccine live may potentiate the replication of the vaccine virus, increase the side/adverse effects of the vaccine virus, and/or decrease the patient's antibody response to measles and rubella virus vaccine live. The interaction may be severe enough to cause death. The interval between discontinuing medications that cause immunosuppression and regaining the ability to respond to measles and rubella virus vaccine live depends on the intensity and type of immunosuppressive medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia that is in remission should not receive measles and rubella virus vaccine live until at least 3 months after the last dose of chemotherapy. The precaution does not apply to corticosteroids used as replacement therapy, for short-term [less than 2 weeks] systemic therapy, or by other routes of administration that do not cause immunosuppression ^{{01} {03}})


Live virus vaccines, other    (data are lacking on impairment of antibody responses to rubella, measles, mumps, or oral poliovirus vaccine (OPV) when these vaccines are administered on different days within 1 month of each other; however, OPV and measles, mumps, and rubella virus vaccine [or its component vaccines] can be administered at any time before, with, or after each other, if indicated ^{53})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
» Tuberculin skin test    (short-term suppression of tuberculin skin test results lasting several weeks may occur and may result in false-negative tests; if required, tuberculin skin tests should be done before, simultaneously with, or at least 4 to 6 weeks ^{53} after administration of measles and rubella virus vaccine live ^{{01} {03}})


Skin tests, other    (decreased responsiveness to skin test antigens may occur because of vaccine-induced transient suppression of delayed-type hypersensitivity; the period of time for which responsiveness is decreased depends upon the particular skin test used)

With physiology/laboratory test values
Platelets, blood    (counts may be decreased)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Febrile illness, severe    (manifestations of illness may be confused with possible side/adverse effects of vaccine; however, minor illnesses, such as upper respiratory infection, do not preclude administration of vaccine ^{{05} {11} {23} {45}})


» Immune deficiency conditions, congenital or hereditary, family history of or
» Immune deficiency conditions, primary or acquired    (because of reduced or suppressed defense mechanisms, the use of live virus vaccines, including measles and rubella virus vaccine live, may potentiate the replication of the vaccine virus, and/or may decrease the patient's antibody response to measles and rubella ^{{01} {02} {03} {04} {06}})

    (persons with leukemia in remission may receive live virus vaccines if at least 3 months have passed since the last chemotherapy treatment ^{{01} {02} {03} {04}})

    (persons infected with HIV may receive measles and rubella virus vaccine live if they are not severely lymphopenic ^{48})

    (when there is a family history of congenital or hereditary immune deficiency conditions, the patient should not be vaccinated until immunocompetence is demonstrated ^{{01} {02} {03} {04}})


Risk-benefit should be considered when the following medical problems exist
Allergy to eggs or
Allergy to neomycin    (a history of hypersensitivity reactions generally does not preclude immunization. Anaphylaxis due to topically or systemically administered neomycin precludes immunization ^{53}. The vaccine may be administered to egg-allergic children without prior skin testing or the use of protocols requiring gradually increasing doses of vaccine ^{53}. In addition, no allergy to measles and rubella virus vaccine has been found in patients allergic to chicken feathers or chicken ^{{01} {22}})


Allergy to gelatin    (patients allergic to gelatin also may be allergic to measles and rubella virus vaccine live, since gelatin is used as a stabilizer in the production of the vaccine ^{52})


Sensitivity to measles and rubella virus vaccine live
Thrombocytopenia or history of vaccine-associated thrombocytopenia    (persons who experienced thrombocytopenia with the first dose of vaccine may develop thrombocytopenia with additional doses ^{52}. These persons should have serologic testing performed in order to determine the need for additional doses of vaccine ^{52}. The risk-benefit ratio should be evaluated before considering vaccination in such cases ^{52})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Seroconversion test    (may be performed 6 to 8 weeks following vaccination in patients for whom immunity is considered crucial [e.g., persons traveling outside the U.S. or women in high-risk areas who intend to become pregnant], since vaccination with measles and rubella virus vaccine may not result in seroconversion in all susceptible patients ^{01})




Side/Adverse Effects

Note: The side/adverse effects associated with the use of measles and rubella virus vaccine live are those expected to follow administration of the monovalent vaccines given separately ^{01}. However, it is very important to differentiate between vaccine-induced side/adverse effects and natural infection ^{30}.
Revaccination of prior vaccinees appears to be associated with relatively low side/adverse effect rates ^{28}.
The incidence of side/adverse effects increases with age and is generally higher in females ^{01}.
A history of hypersensitivity reactions other than anaphylaxis, such as delayed-type allergic reaction (contact dermatitis), generally does not preclude immunization ^{{01} {24}}. There is a very small chance of an adverse reaction in any child, and a study showed that measles- and rubella-containing combined vaccines such as measles, mumps, and rubella virus vaccine live can be administered safely in a single dose to children allergic to eggs, even those with severe hypersensitivity ^{24}.
Encephalitis and encephalopathy have been temporally related to measles vaccine administration and occur in one per million doses administered; however, no causal relationship has been established. The incidence of these diseases after a natural measles infection is one per thousand persons ^{{01} {03}}.
Although there is a temporal relationship, no definite causal relationship has been established between the isolated reports of the occurrence of Guillain-Barré syndrome (GBS) or ocular palsies following the administration of measles vaccine. Isolated incidents of GBS also have been reported after immunization with rubella-containing vaccines ^{{01} {02} {03} {04}}.
It is not known whether some of the cases of subacute sclerosing panencephalitis (SSPE) attributed to the measles virus vaccine were actually due to unrecognized natural measles infection during the first year of life. However, the use of measles virus vaccine has reduced the incidence of SSPE from between 5 and 10 cases per million cases of natural measles infection to 1 case per million doses of measles virus vaccine ^{{01} {02} {03}}.
Persons who are immune to measles and/or rubella virus because of past vaccination or infection usually do not experience side/adverse effects from the vaccine ^{{01} {02} {03} {04}}.
Excretion of small amounts of the live attenuated rubella virus from the nose or throat has occurred in the majority of susceptible individuals 7 to 28 days after vaccination. There is, however, no confirmed evidence to indicate that the vaccine virus is transmitted to susceptible persons who are in contact with the vaccinated individuals ^{04}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Fever over 39.4 ºC (103 ºF)^{01}

Incidence less frequent
    
Optic neuritis (pain or tenderness of eyes)—may occur from 1 to 4 weeks after immunization, lasting less than 1 week^{01}

Incidence rare
    
Anaphylactic reaction (difficulty in breathing or swallowing; hives; itching, especially of feet and hands; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; unusual tiredness or weakness, sudden and severe^{01}{20})
    
encephalitis or meningoencephalitis (confusion; headache, severe or continuing; irritability; stiff neck; vomiting^{{01}{12}{15}{18}{21}})
    
ocular palsies (double vision^{01})
    
peripheral neuropathy, polyneuritis, or polyneuropathy (pain, numbness, or tingling of hands, arms, legs, or feet^{01})—may occur from 1 to 4 weeks after immunization, lasting less than 1 week
    
thrombocytopenic purpura (bruising or purple spots on skin^{01})



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Fever between 37.7 and 39.4 ºC (100 and 103 ºF)^{01}
    
lymphadenopathy or parotitis (swelling of glands in neck)—may occur from 1 to 4 weeks after immunization, lasting less than 1 week^{01}
    
reaction to acid pH of vaccine (burning or stinging at injection site^{01})
    
skin rash^{01}{15}

Incidence less frequent
    
Allergic reaction, delayed-type, cell-mediated (itching, swelling, redness, tenderness, or hard lump at place of injection)
    
arthralgia or arthritis (aches or pain in joint)—may occur from 1 to 10 weeks after immunization, lasting less than 1 week^{{01}{03}{04}{15}}
    
malaise (vague feeling of bodily discomfort)—may occur from 1 to 4 weeks after immunization, lasting less than 1 week
    
mild headache, sore throat, or runny nose —may occur from 1 to 4 weeks after immunization, lasting less than 1 week
    
nausea^{01}

Note: One study showed that the RA 27/3 strain of rubella vaccine administered to susceptible ^{48} adult women is not associated with clinically important acute or chronic joint disease ^{29}. Therefore, rubella vaccination should continue to be used to protect susceptible adult women from rubella in order to advance the goal of eliminating the congenital rubella syndrome ^{29}. The incidence of arthralgia or arthritis is greatly increased in women ^{40} of childbearing age. Generally the older the female, the greater the incidence, severity, and duration of arthralgia or arthritis. However, even in older women, the symptoms are generally well tolerated and rarely interfere with normal activities. No persistent joint disorders ^{{48} {49}} have been reported ^{{01} {03} {04}}.






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Measles and Rubella Virus Vaccine Live (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before receiving this vaccine
»   Conditions affecting use, especially:
Sensitivity to measles and rubella virus vaccine live, or allergy to eggs, gelatin, or neomycin

Pregnancy—Use of measles and rubella virus vaccine live during pregnancy or pregnancy within 3 months of immunization is not recommended





Use in children—Use is not recommended for infants up to 12 months of age, unless risk of measles infection is high

Other medications, especially immunosuppressive agents or radiation therapy
Other medical problems, especially severe febrile illness, family history of congenital or hereditary immune deficiency conditions, or primary or acquired immune deficiency conditions

Proper use of this medication
Waiting at least 14 days after receiving vaccine before receiving blood products or immune globulins ^{53}

Waiting at least 3 to 11 months after administration of blood products or immune globulins before receiving vaccine, depending on the product and dose received ^{53}

» Proper dosing

Precautions after receiving this vaccine
» Not becoming pregnant for 3 months without first checking with physician, because of theoretical ^{53} possibility of birth defects

Checking with physician before receiving tuberculin skin test within 4 to 6 weeks ^{53} of this vaccine, since the results of the test may be affected by the vaccine


Side/adverse effects
Signs of potential side effects, especially fever over 39.4 ºC (103 ºF); optic neuritis; anaphylactic reaction; encephalitis or meningoencephalitis; ocular palsies; peripheral neuropathy, polyneuritis, or polyneuropathy; and thrombocytopenic purpura


General Dosing Information
The dosage of measles and rubella virus vaccine live is the same for both children and adults ^{01}.

Measles and rubella virus vaccine live is administered subcutaneously ^{{01} {05}}. It should not be injected intravenously ^{01}.

When sterilizing syringes and skin before vaccination, care should be taken to avoid preservatives, antiseptics, detergents, and disinfectants because the vaccine virus is easily inactivated by these substances ^{01}.

To prevent inactivation of the vaccine, it is recommended that only the diluent provided by the manufacturer be used ^{01}.

A 25-gauge, 5/8th-inch needle is recommended for administration of the vaccine ^{{01} {05}}.

Although measles and rubella vaccines are available as a combination vaccine (measles and rubella virus vaccine live) and, as such, are administered as a single injection, the commercially available individual vaccines should not be mixed in the same syringe or administered at the same body site ^{01}.

Although the fourth dose of diphtheria, tetanus, and pertussis (DTP) vaccine and the third dose of oral poliovirus vaccine (OPV) traditionally have been administered to children 18 months of age and a measles-containing vaccine (preferably as measles, mumps, and rubella virus vaccine live) traditionally has been administered to children 15 months of age, it is now recommended that DTP, OPV, and measles, mumps, and rubella virus vaccine live be administered concurrently to children 12 to 15 months of age. Measles, mumps, and rubella virus vaccine live should not be postponed in order to administer all of these vaccines concurrently at 18 months of age ^{05}.
Measles and rubella virus vaccine, a live virus vaccine, may be administered concurrently with the following, using separate body sites, separate syringes, and the precautions that apply to each immunizing agent:

   • Polysaccharide vaccines, such as Haemophilus b conjugate vaccine, Haemophilus b polysaccharide vaccine, meningococcal polysaccharide vaccine, or pneumococcal polyvalent vaccine ^{05}.
   • Influenza vaccine, whole or split virus ^{05}.
   • Diphtheria toxoid, tetanus toxoid, and/or pertussis vaccine ^{05}.
   • Live virus vaccines, other, such as OPV and varicella ^{{35} {36} {37}}. OPV and measles, mumps, and rubella virus vaccine (or its component vaccines) can be administered at any time before, with, or after each other, if indicated ^{53}.
   • Inactivated poliovirus vaccine (IPV) or enhanced-potency inactivated poliovirus vaccine (enhanced-potency IPV) ^{05}.
   • Hepatitis B recombinant or plasma-derived vaccine ^{05}.
   • Inactivated vaccines, other, except cholera, plague, and typhoid. It is recommended that cholera, plague, and typhoid vaccines be administered on separate occasions because of these vaccines' propensity to cause side/adverse effects ^{05}.

For treatment of adverse effects
Recommended treatment consists of the following:
   • For mild hypersensitivity reaction—Administering antihistamines, and, if necessary, corticosteroids.
   • For severe hypersensitivity or anaphylactic reaction—Administering epinephrine. Antihistamines or corticosteroids also may be administered as required.


Parenteral Dosage Forms

MEASLES AND RUBELLA VIRUS VACCINE LIVE (FOR INJECTION) USP

Usual adult and adolescent dose
Immunizing agent (active)
Subcutaneous, 0.5 mL, preferably into the outer aspect of the upper arm ^{01}.


Usual pediatric dose
Immunizing agent (active)
Infants up to 12 months of age: Use is not recommended.

Infants and children 12 to 15 months of age and older: See Usual adult and adolescent dose ^{{05} {46}}.


Note: The Committee on Infectious Diseases of the American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) recommend that all children receive a second dose of measles-containing vaccine ^{46}. The second dose of measles-containing vaccine (preferably as measles, mumps, and rubella virus vaccine live) is routinely recommended at 4 to 6 years of age, but may be administered at any visit, provided at least one month has elapsed since receipt of the first dose ^{{10} {39}}. The preadolescent health visit at 11 to 12 years of age can serve as a catch up opportunity to verify vaccination status and administer the vaccine to those children who have not yet received two doses of a measles-containing vaccine ^{53}.


Strength(s) usually available
U.S.—


Not less than the equivalent of 1000 median tissue culture infective dose [TCID ₅₀] of the U.S. Reference Measles Virus and not less than the equivalent of 1000 TCID ₅₀ of the U.S. Reference Rubella Virus in each 0.5-mL dose (Rx) [M-R-VAX II (neomycin approximately 25 mcg^{01})]

Canada—
Not commercially available.

Packaging and storage:
Store the lyophilized form of the vaccine, the diluent, and the reconstituted form of the vaccine between 2 and 8 ºC (36 and 46 ºF), unless otherwise specified by manufacturer ^{{01} {09}}.

Alternatively, the diluent for the single-dose vials may be stored between 15 and 30 ºC (59 and 86 ºF) ^{01}.

Protect both the lyophilized form and the reconstituted form of the vaccine from light ^{{01} {09}}.

Preparation of dosage form:
To reconstitute, use only the diluent provided by the manufacturer, since it is free of preservatives and other substances that might inactivate the vaccine ^{01}.

Single-dose vial—The entire volume of diluent (approximately 0.5 mL) should be withdrawn into the syringe. All the diluent in the syringe should be injected into the vial of lyophilized vaccine and agitated to mix thoroughly. The entire contents of the vial should be withdrawn into the syringe and the total volume of restored vaccine injected subcutaneously ^{01}.

10-dose vial (in U.S., available only to government agencies/institutions)—The entire contents (7 mL) of the diluent vial should be withdrawn into the syringe to be used for reconstitution. All of the diluent in the syringe should be injected into the 10-dose vial of lyophilized vaccine and agitated to mix thoroughly. The 10-dose container can be used with either syringes or a jet injector. Since the vaccine and diluent do not contain preservatives, special care should be taken to prevent contamination of the multiple-dose vial of vaccine. In addition, the vial should be stored properly until the reconstituted vaccine is used. Unused vaccine should be discarded after 8 hours ^{01}.

50-dose vial (in U.S., available only to government agencies/institutions)—The entire contents (30 mL) of the diluent vial should be withdrawn into the syringe to be used for reconstitution. All of the diluent in the syringe should be injected into the 50-dose vial of lyophilized vaccine and agitated to mix thoroughly. The 50-dose container is designed to be used only with a jet injector. Since the vaccine and diluent do not contain preservatives, special care should be taken to prevent contamination of the multiple-dose vial of vaccine. In addition, the vial should be stored properly until the reconstituted vaccine is used. Unused vaccine should be discarded after 8 hours ^{01}.

Stability:
Both the lyophilized and the reconstituted vaccine should be stored between 2 and 8 ºC (36 and 46 ºF) and protected from light. Improper storage and protection may inactivate the vaccine ^{{01} {09}}.

The reconstituted vaccine should be used as soon as possible. Unused reconstituted vaccine should be discarded after 8 hours ^{{01} {09}}.

The reconstituted vaccine is clear yellow. It should not be used if it is discolored ^{01}.

Incompatibilities:
Preservatives or other substances may inactivate the vaccine; therefore, only the diluent supplied by the manufacturer should be used for reconstitution ^{01}.

A sterile syringe free of preservatives, antiseptics, disinfectants, and detergents should be used for each injection and/or reconstitution of the vaccine. These substances may inactivate the live virus vaccine ^{01}.

Auxiliary labeling:
   • Protect from light.
   • Store in refrigerator ^{01}.
   • Discard reconstituted vaccine if not used within 8 hours ^{{01} {09}}.

Note: The date and the time of reconstitution should be indicated on the vial if the reconstituted vaccine is not used at once.

Revised: 04/29/1997

References

1. M-R-VAX II package insert (Merck—US), Rev 3/95, Rec 1/96.
   

2. Attenuvax package insert (Merck—US), Rev 3/95, Rec 1/96.
   

3. M-M-R II package insert (Merck—US), Rev 3/95, Rec 1/96.
   

4. Meruvax package insert (Merck—US), Rev 3/95, Rec 2/96.
   

5. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): general recommendations on immunization. MMWR Morb Mortal Wkly Rep 1994; 43(RR-1): 1-38.
   

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

7. Centers for Disease Control and Prevention. Recommendations of the International Task Force for Disease Eradication. MMWR Morb Mortal Wkly Rep 1993; 42(RR-16): 1-38.
   

8. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): rubella prevention. MMWR Morb Mortal Wkly Rep 1990; 39(RR-15): 1-18.
   

9. The United States pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 934.
   

10. Centers for Disease Control and Prevention. Immunization of adolescents—Recommendations of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association. MMWR Morb Mortal Wkly Rep 1996; 45(RR-13): 3.
    

11. 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(9): 704-7.
    

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13. Arya SC. Human immunization in developing countries: practical and theoretical problems and prospects. Vaccine 1994; 12(15): 1423-35.
    

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15. Carter H, Campbell H. Rational use of measles, mumps and rubella (MMR) vaccine. Drugs 1993; 45(5): 677-83.
    

16. Krober MS, Stracener CE, Bass JW. Decreased measles antibody response after measles-mumps-rubella vaccine in infants with colds. JAMA 1991; 265(16): 2095-6.
    

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(2): 269-71.
    

18. Crowley S, Al-Jawad ST, Kovar IZ. Measles, mumps, and rubella vaccination and encephalitis. BMJ 1989; 299: 660.
    

19. Puvvada L, Silverman B, Bassett C, et al. Systemic reactions to measles-mumps-rubella vaccine skin testing. Pediatrics 1993; 91(4): 835-6.
    

20. Kelso JM, Jones RT, Yunginger JW. Anaphylaxis to measles, mumps, and rubella vaccine mediated by IgE to gelatin. J Allergy Clin Immunol 1993; 867-72.
    

21. Griffin MR, Ray WA, Mortimer EA, et al. Risk of seizures after measles-mumps-rubella immunization. Pediatrics 1991; 88(5): 881-5.
    

22. Beck SA, Williams LW, Shirrell MA. Egg hypersensitivity and measles-mumps-rubella vaccine administration. Pediatrics 1991; 88(5): 913-7.
    

23. Weber DJ, Rutala WA, Orenstein WA. Prevention of mumps, measles, and rubella among hospital personnel. J Pediatr 1991; 119(2): 322-6.
    

24. James JM, Burks AW, Robertson PK, et al. Safe administration of the measles vaccine to children allergic to eggs. N Engl J Med 1995; 332: 1262-6.
    

25. Christenson B, Böttiger M. Measles antibody: comparison of long-term vaccination titers, early vaccination titers and naturally acquired immunity to and booster effects on the measles virus. Vaccine 1994; 12(2): 129-33.
    

26. Fennelly GJ, Flynn JL, Meulen VT, et al. Recombinant BCG priming against measles. J Infect Dis 1995; 172: 698-705.
    

27. Christenson B, Böttiger M. Long-term follow-up study of rubella antibodies in naturally immune and vaccinated young adults. Vaccine 1994; 12(1): 41-5.
    

28. Seager C, Moriarity J, Ngai A, et al. Low incidence of adverse experiences after measles or measles-rubella mass revaccination at a college campus. Vaccine 1994; 12(11): 1018-20.
    

29. Slater PE, Ben-Zvi T, Fogel A, et al. Absence of an association between rubella vaccination and arthritis in underimmune postpartum women. Vaccine 1995; 13(16): 1529-32.
    

30. Kobune F, Funatu M, Takahashi H, et al. Characterization of measles viruses isolated after measles vaccination. Vaccine 1995; 13(4): 370-2.
    

31. de Quadros CA, Olivé JM, Hersh BS, et al. Measles elimination in the Americas: evolving strategies. JAMA 1996; 275(3): 224-9.
    

32. Chen RT, Markowitz LE, Albrecht P, et al. Measles antibody: Reevaluation of protective titers. J Infect Dis 1990; 162: 1036-42.
    

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34. Hilton E, Singer C, Kozarsky P, et al. Status of immunity to tetanus, measles, mumps, rubella, and polio among U.S. travelers. Ann Intern Med 1991; 115: 32-3.
    

35. Varivax package insert (Merck—US), Rev 3/95, Rec 4/96.
    

36. Isaacs D, Menser M. Measles, mumps, rubella, and varicella. Lancet 1990; 335: 1384-7.
    

37. Watson BM, Laufer DS, Kuter BJ, et al. Safety and immunogenicity of a combined live attenuated measles, mumps, rubella, and varicella vaccine (MMR II V) in healthy children. J Infect Dis 1996; 173: 731-4.
    

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40. Preblud SR. Some current issues relating to rubella vaccine. JAMA 1985 254(2): 253-6.
    

41. Centers for Disease Control and Prevention. Rubella vaccination during pregnancy—United States, 1971–1986. JAMA 1987; 258(6): 753, 757.
    

42. Atmar RL, Englund JA, Hammill H. Complications of measles during pregnancy. Clin Infect Dis 1992; 14: 217-26.
    

43. Wittler RR, Veit BC, McIntyre S, et al. Measles revaccination response in a school-age population. Pediatrics 1991; 88(5): 1024-30.
    

44. Sha BE, Harris AA, Benson CA, et al. Prevalence of measles antibodies in asymptomatic human immunodeficiency virus–infected adults. J Infect Dis 1991; 164: 973-5.
    

45. Dennehy PH, Saracen CL, Peter G. Seroconversion rates to combined measles, mumps, rubella, and varicella of children with upper respiratory tract infection. Pediatrics 1994; 94: 514-6.
    

46. Centers for Disease Control and Prevention. Recommended childhood immunization schedule—United States, 1995. MMWR Morb Mortal Wkly Rep 1995; 44(RR-5): 1-9.
    

47. Measles, mumps, and rubella vaccine: an essential drug [editorial]. Drugs 1993; 2(7): 1-4.
    

48. Panel comment, 10/96.
    

49. Panel comment, 10/96.
    

50. Panel comment, 10/96.
    

51. Panel comment, 10/96.
    

52. Reviewer comment, 10/96.
    

53. Reviewer comment, 2/97.
    

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