1.  Centers for Disease Control and Prevention (CDC). Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010;59(RR-3):1–12.
2.  Centers for Disease Control and Prevention (CDC). Home. Vaccines for Children Program (VFC)
Web site. http://www.cdc.gov/vaccines/programs/
vfc/index.html. Updated April 24, 2014. Accessed
March 2, 2016.
3.  Centers for Disease Control and Prevention (CDC).
About VFC. Vaccines for Children Program (VFC)
Web site. http://www.cdc.gov/vaccines/programs/
vfc/about/index.html. Updated February 14, 2014. Accessed March 2, 2016.
4.  Centers for Disease Control and Prevention (CDC). VFC Detailed Questions and Answers for Parents. Vaccines for Children Program (VFC) Web site. http://www.cdc.gov/vaccines/programs/vfc/parents/
qa-detailed.html. Updated February 19, 2013. Accessed March 2, 2016.

Indication for ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live)

ProQuad is a vaccine indicated for active immunization for the prevention of measles, mumps, rubella, and varicella in children 12 months through 12 years of age.

Selected Safety Information for ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live)

ProQuad is contraindicated in individuals with any of the following: history of anaphylactic reaction to neomycin or hypersensitivity to gelatin or any other component of the vaccine; primary or acquired immunodeficiency states; family history of congenital or hereditary immunodeficiency; immunosuppressive therapy; active untreated tuberculosis or febrile illness (>101.3°F or >38.5°C); or those who are pregnant. If vaccination of post-pubertal females is undertaken, pregnancy should be avoided for 3 months following vaccination.

Administration of ProQuad (dose 1) to children 12 to 23 months old who have not been previously vaccinated against measles, mumps, rubella, or varicella, nor had a history of the wild-type infections, is associated with higher rates of fever and febrile seizures at 5 to 12 days after vaccination when compared to children vaccinated with dose 1 of both M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live) and VARIVAX® (Varicella Virus Vaccine Live) administered separately.

Use caution when administering ProQuad to children with: a history of cerebral injury or seizures or any other condition in which stress due to fever should be avoided; anaphylaxis or immediate hypersensitivity to eggs; contact hypersensitivity to neomycin; thrombocytopenia. Children with immediate hypersensitivity to eggs may be vaccinated with extreme caution; adequate treatment should be readily available should a reaction occur.

Advise vaccinees to avoid: close contact with high-risk individuals susceptible to varicella for up to 6 weeks following vaccination since transmission of varicella vaccine virus may occur between vaccinees and susceptible contacts; pregnancy for 3 months after vaccination; using salicylates for 6 weeks after vaccination. Defer vaccination for at least 3 months following blood or plasma transfusions, or administration of immune globulins (IG). The appropriate suggested interval between transfusion or IG administration and vaccination will vary with the type of transfusion or indication for, and dose of, IG.

Following administration of ProQuad, any immune globulin (IG), including VZIG, should not be given for 1 month thereafter unless its use outweighs the benefits of vaccination.

The most frequent vaccine-related adverse events reported in ≥5% of subjects vaccinated with ProQuad were: injection-site reactions (pain/tenderness/soreness, erythema, and swelling); fever; and irritability. Systemic vaccine-related adverse events that were reported at a significantly greater rate in recipients of ProQuad than in recipients of the component vaccines administered concomitantly were fever and measles-like rash. In children 12 to 23 months of age, the only vaccine-related injection-site adverse reaction that was more frequent among recipients of ProQuad than recipients of M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine, Live) and VARIVAX® (Varicella Virus Vaccine Live) was rash at the injection site (2.4% versus 1.6%, respectively).

Dosage and Administration for ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live)

Each 0.5 mL dose of ProQuad is administered subcutaneously.

  • The first dose is usually administered at 12 to 15 months of age.
  • A second dose, if needed, is usually administered at 4 to 6 years of age.

At least 1 month should elapse between a dose of a measles-containing vaccine such as M-M-R®II and a dose of ProQuad. At least 3 months should elapse between a dose of varicella-containing vaccine and ProQuad.

No clinical data are available regarding the development or worsening of thrombocytopenia in individuals vaccinated with ProQuad. Cases of thrombocytopenia have been reported after primary vaccination with measles vaccine; measles, mumps, rubella vaccine; after varicella vaccination; and following revaccination with measles vaccine or M-M-R®II.

The safety and efficacy of ProQuad for use after exposure to measles, mumps, rubella or varicella have not been established.

The safety and efficacy of ProQuad for use in children known to be infected with human immunodeficiency viruses have not been established.

In severely immunocompromised individuals who have been inadvertently vaccinated with measles containing vaccine, measles inclusion body encephalitis, pneumonitis and fatal outcome as a direct consequence of disseminated measles vaccine virus infection have been reported. In this population, disseminated mumps and rubella vaccine virus infection have also been reported.

Tuberculin testing should be administered anytime before, simultaneously with, or at least 4 to 6 weeks after ProQuad.

ProQuad may be administered concomitantly with pneumococcal 7-valent conjugate vaccine and/or hepatitis A vaccine (inactivated) at separate injection sites.

ProQuad may be administered concomitantly with Haemophilus influenzae type b conjugate (meningococcal protein conjugate) and hepatitis B (recombinant) vaccine. Additionally, ProQuad may be administered concomitantly with pneumococcal 7-valent conjugate vaccine, and/or hepatitis A (inactivated) vaccines.

There are no data regarding the administration of ProQuad with inactivated poliovirus vaccine or with other live virus vaccines.

There are insufficient data to support concomitant vaccination with diphtheria, tetanus, and acellular pertussis vaccine adsorbed.

The duration of protection from measles, mumps, rubella, and varicella infections after vaccination with ProQuad is unknown.

Before administering ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live), please read the Prescribing Information.

Recommendations for ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live)

The ACIP recommends ProQuad as its general preference for the routine 2nd dose1

1ST DOSE (12–15 months of age)

ACIP recommendations

The ACIP recommends that M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live) and VARIVAX® (Varicella Virus Vaccine Live) be administered unless a parent or caregiver expresses a preference for ProQuad, the combination vaccine.

2ND DOSE (4–6 years of age)

ACIP recommendations

The ACIP generally prefers ProQuad to separate injections of its equivalent component vaccines,
M-M-R®II and VARIVAX.




ACIP=Advisory Committee on Immunization Practices.

ACIP preference for 1st dose (routinely given at 12–15 months of age)1,a

Baby with Teddybear
  • The ACIP recommends that M-M-R®II and VARIVAX be administered as separate injections, unless the parent/caregiver expresses a preference for ProQuad at 1st dose.1
  • ProQuad is associated with a higher relative risk of febrile seizures at 5 to 12 days after vaccination compared with M-M-R®II and VARIVAX administered concomitantly. In a postmarketing observational safety surveillance study of children 12 to 60 months of age (N=31,298, including 31,043 who were 12 to 23 months old), the incidence of febrile seizures 5 to 12 days after ProQuad administered at Dose 1 (0.70 per 1,000 children) was higher than that in children (N=31,298, including 31,019 who were 12 to 23 months old) receiving M-M-R®II and VARIVAX concomitantly (0.32 per 1,000 children) [RR 2.20 (95% CI: 1.04, 4.65)].
  • If you are considering ProQuad for the 1st dose, the ACIP recommends that you discuss the benefits and risks of both options with the parent/caregiver.1
  • A personal or family history of seizures of any etiology is a precaution for vaccination with ProQuad.1
 
aThe ACIP generally prefers ProQuad for the 1st dose at age ≥48 months.1
ACIP=Advisory Committee on Immunization Practices; CI=confidence interval; RR=relative risk.

ACIP preference for 2nd dose (routinely given at 4–6 years of age)1

Boy with Teddybear
  • The ACIP generally prefers ProQuad for the 2nd dose at any age (15 months to 12 years).1
  • In a postmarketing observational study, no cases of febrile seizure were observed during the 5- to 12-day postvaccination period among children (n=26,455) who received ProQuad as a 2nd dose.
  • A personal or family history of seizures of any etiology is a precaution for vaccination with ProQuad.1
ACIP=Advisory Committee on Immunization Practices.
 

See Indication and Selected Safety Information for M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live) and VARIVAX® (Varicella Virus Vaccine Live) below.

Indication for ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live)

ProQuad is a vaccine indicated for active immunization for the prevention of measles, mumps, rubella, and varicella in children 12 months through 12 years of age.

Selected Safety Information for ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live)

ProQuad is contraindicated in individuals with any of the following: history of anaphylactic reaction to neomycin or hypersensitivity to gelatin or any other component of the vaccine; primary or acquired immunodeficiency states; family history of congenital or hereditary immunodeficiency; immunosuppressive therapy; active untreated tuberculosis or febrile illness (>101.3°F or >38.5°C); or those who are pregnant. If vaccination of post-pubertal females is undertaken, pregnancy should be avoided for 3 months following vaccination.

Administration of ProQuad (dose 1) to children 12 to 23 months old who have not been previously vaccinated against measles, mumps, rubella, or varicella, nor had a history of the wild-type infections, is associated with higher rates of fever and febrile seizures at 5 to 12 days after vaccination when compared to children vaccinated with dose 1 of both M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live) and VARIVAX® (Varicella Virus Vaccine Live) administered separately.

Use caution when administering ProQuad to children with: a history of cerebral injury or seizures or any other condition in which stress due to fever should be avoided; anaphylaxis or immediate hypersensitivity to eggs; contact hypersensitivity to neomycin; thrombocytopenia. Children with immediate hypersensitivity to eggs may be vaccinated with extreme caution; adequate treatment should be readily available should a reaction occur.

Advise vaccinees to avoid: close contact with high-risk individuals susceptible to varicella for up to 6 weeks following vaccination since transmission of varicella vaccine virus may occur between vaccinees and susceptible contacts; pregnancy for 3 months after vaccination; using salicylates for 6 weeks after vaccination. Defer vaccination for at least 3 months following blood or plasma transfusions, or administration of immune globulins (IG). The appropriate suggested interval between transfusion or IG administration and vaccination will vary with the type of transfusion or indication for, and dose of, IG.

Following administration of ProQuad, any immune globulin (IG), including VZIG, should not be given for 1 month thereafter unless its use outweighs the benefits of vaccination.

The most frequent vaccine-related adverse events reported in ≥5% of subjects vaccinated with ProQuad were: injection-site reactions (pain/tenderness/soreness, erythema, and swelling); fever; and irritability. Systemic vaccine-related adverse events that were reported at a significantly greater rate in recipients of ProQuad than in recipients of the component vaccines administered concomitantly were fever and measles-like rash. In children 12 to 23 months of age, the only vaccine-related injection-site adverse reaction that was more frequent among recipients of ProQuad than recipients of M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine, Live) and VARIVAX® (Varicella Virus Vaccine Live) was rash at the injection site (2.4% versus 1.6%, respectively).

Dosage and Administration for ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live)

Each 0.5 mL dose of ProQuad is administered subcutaneously.

  • The first dose is usually administered at 12 to 15 months of age.
  • A second dose, if needed, is usually administered at 4 to 6 years of age.

At least 1 month should elapse between a dose of a measles-containing vaccine such as M-M-R®II and a dose of ProQuad. At least 3 months should elapse between a dose of varicella-containing vaccine and ProQuad.

No clinical data are available regarding the development or worsening of thrombocytopenia in individuals vaccinated with ProQuad. Cases of thrombocytopenia have been reported after primary vaccination with measles vaccine; measles, mumps, rubella vaccine; after varicella vaccination; and following revaccination with measles vaccine or M-M-R®II.

The safety and efficacy of ProQuad for use after exposure to measles, mumps, rubella or varicella have not been established.

The safety and efficacy of ProQuad for use in children known to be infected with human immunodeficiency viruses have not been established.

In severely immunocompromised individuals who have been inadvertently vaccinated with measles containing vaccine, measles inclusion body encephalitis, pneumonitis and fatal outcome as a direct consequence of disseminated measles vaccine virus infection have been reported. In this population, disseminated mumps and rubella vaccine virus infection have also been reported.

Tuberculin testing should be administered anytime before, simultaneously with, or at least 4 to 6 weeks after ProQuad.

ProQuad may be administered concomitantly with pneumococcal 7-valent conjugate vaccine and/or hepatitis A vaccine (inactivated) at separate injection sites.

ProQuad may be administered concomitantly with Haemophilus influenzae type b conjugate (meningococcal protein conjugate) and hepatitis B (recombinant) vaccine. Additionally, ProQuad may be administered concomitantly with pneumococcal 7-valent conjugate vaccine, and/or hepatitis A (inactivated) vaccines.

There are no data regarding the administration of ProQuad with inactivated poliovirus vaccine or with other live virus vaccines.

There are insufficient data to support concomitant vaccination with diphtheria, tetanus, and acellular pertussis vaccine adsorbed.

The duration of protection from measles, mumps, rubella, and varicella infections after vaccination with ProQuad is unknown.

Before administering ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live), please read the Prescribing Information.

About M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live)

M-M-R®II is indicated for simultaneous vaccination against measles, mumps, and rubella in individuals 12 months of age or older.

The ACIP recommends administration of the first dose of M-M-R®II at 12 to 15 months of age and administration of the second dose of M-M-R®II at 4 to 6 years of age.

Selected Safety Information for M-M-R®II

M-M-R®II is contraindicated in certain individuals, including those with: a history of hypersensitivity to any component of the vaccine, including gelatin; a history of anaphylactic or anaphylactoid reaction to neomycin; blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems; primary or acquired immunodeficiency conditions; family history of congenital or hereditary immunodeficiency or receiving immunosuppressive therapy; an active febrile illness; or those who are pregnant. If vaccination of postpubertal females is undertaken, pregnancy should be avoided for 3 months following vaccination.

Due caution should be employed in administration of M-M-R®II to persons with: a history of cerebral injury, individual or family histories of convulsions, or any other condition in which stress due to fever should be avoided; anaphylaxis or immediate hypersensitivity to eggs; thrombocytopenia.

The following adverse reactions have been reported with M-M-R®II without regard to causality: fever, headache, dizziness, rash, injection-site reactions, febrile convulsions, anaphylaxis and anaphylactoid reactions, arthritis, and thrombocytopenia. Additional adverse reactions, which have been reported without regard to causality, include encephalitis and encephalopathy in their diverse clinical presentations.

Vaccination should be deferred for 3 months or longer following blood or plasma transfusions, or administration of immune globulin (human).

As for any vaccine, vaccination with M-M-R®II may not result in protection in 100% of vaccinees.

Dosage and Administration for M-M-R®II

FOR SUBCUTANEOUS ADMINISTRATION. Do not inject intravascularly.

Immune globulin (IG) is not to be given concurrently with M-M-R®II.

M-M-R®II should be given one month before or after administration of other live viral vaccines. M-M-R®II has been administered concurrently with VARIVAX® (Varicella Virus Vaccine Live) and PedvaxHIB® [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] using separate injection sites and syringes.

Before administering M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live), please read the Prescribing Information. The Patient Information also is available.

About VARIVAX® (Varicella Virus Vaccine Live)

VARIVAX is a vaccine indicated for active immunization for the prevention of varicella in individuals 12 months of age or older.

Each dose is approximately 0.5 mL after reconstitution and is administered by subcutaneous injection.

Children (12 months to 12 years of age): If a second dose is administered, there should be a minimum interval of 3 months between doses.

Adolescents (≥13 years of age) and Adults: 2 doses, to be administered with a minimum interval of 4 weeks between doses.

Selected Safety Information for VARIVAX

Do not administer VARIVAX to individuals with: a history of severe allergic reaction to any component of the vaccine (including neomycin and gelatin) or to a previous dose of varicella vaccine; immunosuppressed or immunodeficient individuals, including those with a history of primary or acquired immunodeficiency states, leukemia, lymphoma, or other malignant neoplasms affecting the bone marrow or lymphatic system, AIDS, or receiving immunosuppressive therapy; any febrile illness or active infection, untreated tuberculosis; or those who are pregnant.

Evaluate individuals for immune competence prior to administration of VARIVAX if there is a family history of immunodeficiency. Vaccine recipients should avoid contact with high-risk individuals susceptible to varicella due to possible risk of transmission. Defer vaccination for ≥5 months following blood or plasma transfusions or administration of immune globulins. Avoid use of salicylates for 6 weeks following administration of VARIVAX to children and adolescents.

Frequently reported (≥10%) adverse reactions in children ages 1 to 12 years who were monitored for 42 days include: fever ≥102.0°F (38.9°C) oral: 14.7%; injection-site complaints: 19.3%. Frequently reported (≥10%) adverse reactions in adolescents and adults ages 13 years and older monitored for up to 42 days include: fever ≥100.0°F (37.8°C) oral: 10.2%; injection-site complaints: 24.4%. Other reported adverse reactions in all age groups include: varicella-like rash (injection site) and varicella-like rash (generalized).

In a clinical trial involving children who received 2 doses of VARIVAX 3 months apart, the incidence of injection-site clinical complaints (primarily erythema and swelling) observed in the first 4 days following vaccination was slightly higher post-dose 2 (overall incidence 25.4%) than post-dose 1 (overall incidence 21.7%), whereas the incidence of systemic clinical complaints in the 42 day follow-up period was lower post-dose 2 (66.3%) than post-dose 1 (85.8%).

There are insufficient data to assess the rate of protection of VARIVAX against the serious complications of chickenpox in adults (eg, encephalitis, hepatitis, pneumonia), and during pregnancy (congenital varicella syndrome).

The duration of protection from varicella infection after vaccination with VARIVAX is unknown.

Vaccination with VARIVAX may not result in protection of all healthy, susceptible children, adolescents, and adults.

A boost in antibody levels has been observed in vaccinees following exposure to wildtype varicella, which could account for the apparent long-term persistence of antibody levels in these studies.

Due to the concern for transmission of vaccine virus, vaccine recipients should attempt to avoid, whenever possible, close association with susceptible high-risk individuals for up to 6 weeks following vaccination.

VARIVAX is contraindicated for use in pregnant women because the vaccine contains live, attenuated varicella virus, and it is known that wild-type varicella virus, if acquired during pregnancy, can cause congenital varicella.

It is not known whether varicella vaccine virus is excreted in human milk.

Before administering VARIVAX® (Varicella Virus Vaccine Live), please read the Prescribing Information. The Patient Information also is available.

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