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. American Medical Association (AMA). CPT® 2018 Standard Edition (Current Procedural Terminology [Standard]). Chicago, IL: American Medical Association; 2017
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 November 10, 2017.
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 November 10, 2017.

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

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

VARIVAX® (Varicella Virus Vaccine Live) is a vaccine indicated for active immunization for the prevention of varicella in individuals 12 months of age or older.

M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live) is indicated for simultaneous vaccination against measles, mumps, and rubella in individuals 12 months of age or older.

Selected Safety Information for ProQuad

Contraindications: ProQuad, M-M-R®II, and VARIVAX are contraindicated in certain individuals, including those with: primary or acquired immunodeficiency conditions including AIDS; family history of congenital or hereditary immunodeficiency or receiving immunosuppressive therapy; blood dyscrasias; thrombocytopenia; untreated tuberculosis; leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems; an active febrile illness or infection.

Hypersensitivity: ProQuad, M-M-R®II, and VARIVAX are contraindicated in patients with a history of hypersensitivity to any component of the vaccine (gelatin). Children with anaphylaxis or immediate hypersensitivity to eggs may be vaccinated with ProQuad and M-M-R®II with extreme caution and adequate treatment should be readily available should a reaction occur.

Neomycin Precautions: For patients vaccinated with ProQuad and M-M-R®II neomycin allergies most commonly manifest as contact dermatitis, which is not a contraindication to receiving either vaccine. VARIVAX is contraindicated in patients who have a neomycin allergy.

Pregnancy Precautions: ProQuad, M-M-R®II, and VARIVAX are contraindicated for use in pregnant women. If vaccination of postpubertal females is undertaken pregnancy should be avoided for 3 months following vaccination. VARIVAX is a live, attenuated varicella virus, and it is known that wild-type varicella virus, if acquired during pregnancy, can cause congenital varicella.

Febrile Seizures: 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 and VARIVAX administered separately.

Cerebral Injury/Seizures: Use caution when administering ProQuad and M-M-R®II to children with: a history of cerebral injury or seizures or any other condition in which stress due to fever should be avoided.

Varicella Transmission and Precautions: Advise patients administered ProQuad or VARIVAX to avoid: close contact with high-risk individuals susceptible to varicella for up to 6 weeks following vaccination since transmission of varicella vaccine virus to susceptible contacts has been reported.

Immune Globulins and Transfusions: For ProQuad and M-M-R®II defer vaccination for at least 3 months following blood or plasma transfusions, or administration of immune globulins (IG). For VARIVAX, defer vaccination for ≥5 months following blood or plasma transfusions or administration of immune globulins. 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.

Use of Salicylates: Advise patients vaccinated with ProQuad or VARIVAX to avoid use of salicylates for 6 weeks following vaccine administration.

Vaccine-related Adverse Events: The following have been reported for ProQuad, M-M-R®II, and VARIVAX: injection-site reactions (pain/tenderness/soreness, erythema, and swelling); irritability; and rash on the body or at the injection site. 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.

VARIVAX Dose-related Adverse Events: In a clinical trial involving children who received 2 doses of VARIVAX® 3 months apart, the incidence of injection-site clinical complaints 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%).

Concomitant Vaccines With ProQuad: ProQuad may be administered concomitantly with Haemophilus influenzae type b conjugate (meningococcal protein conjugate) and hepatitis B (recombinant) vaccine. It may also be administered concomitantly with pneumococcal 7-valent conjugate vaccine and/or hepatitis A vaccine (inactivated) at separate injection sites. There are insufficient data to support concomitant vaccinations with the diphtheria, tetanus, and acellular pertussis vaccine adsorbed and no data regarding the administration of ProQuad with inactivated poliovirus vaccine or with other live virus vaccines.

Tuberculin Testing: If a tuberculin test is to be done with M-M-R®II and ProQuad, it should be administered either any time before, simultaneously with, or at least 4 to 6 weeks after vaccination. With VARIVAX, tuberculin testing may be performed before the vaccine is administered or at least 4 weeks following vaccination.

Additional ProQuad Precautions: No clinical data are available regarding the development or worsening of thrombocytopenia in individuals vaccinated with ProQuad. The safety and efficacy of ProQuad for use in children known to be infected with human immunodeficiency viruses and after exposure to measles, mumps, rubella, or varicella have not been established.

Additional M-M-R®II Precautions: Additional adverse reactions, which have been reported without regard to causality, include, febrile convulsions, arthritis, thrombocytopenia, encephalitis and encephalopathy in their diverse clinical presentations.

Additional VARIVAX Precautions: There are insufficient data to assess the rate of protection of VARIVAX against the serious complications of chickenpox in adults (eg, encephalitis, hepatitis, pneumonia), during pregnancy. It is also not known if varicella vaccine virus is excreted in human milk. A boost in antibody levels has been observed in vaccinees following exposure to wild-type varicella, which could account for the apparent long-term persistence of antibody levels in studies. The duration of protection from varicella infection after vaccination is unknown.

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

Dosage And Administration for ProQuad
ProQuad:

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.

VARIVAX:

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.

M-M-R®II:

The dose for any age is 0.5 mL administered subcutaneously.

The recommended age for primary vaccination is 12 to 15 months and the second dose should be given at 4 to 6 years of age.

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

After 2nd MMRV
vaccine dose,
in a
large observational
study,
no incidence
of febrile seizures

After 2nd MMRV Vaccine Dose, in a Large Observational Study, No Incidence of Febrile Seizures
Incidence of febrile seizure with
ProQuad vs M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live) + VARIVAX® (Varicella Virus Vaccine Live) per 1000 children 12 months to 12 years of age.

1ST DOSE

5-12 days
postvaccination

0.70

ProQuad

vs

0.32

M-M-R®II + VARIVAX

RR=2.20 (95% CI: 1.04, 4.65)
(N=31,298; 31,019 were
between
12 and 23 months
of age)

0-30 days
postvaccination

1.41

ProQuad

vs

1.28

M-M-R®II + VARIVAX

RR=1.10 (95% CI: 0.72, 1.69)
(N=31,298)

2ND DOSE

5-12 days
postvaccination

0

cases in children
who received ProQuad

(N=26,455)

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 and VARIVAX
administered separately.

Safety was evaluated in an observational study that included 69,237 children aged 12 months to 12 years vaccinated with ProQuad after 1st dose with M-M-R®II + VARIVAX. A historical comparison group included 69,237 age-, gender-, and date-of-vaccination (day and month) matched subjects who were given M-M-R®II and VARIVAX concomitantly. The primary objective was to assess the incidence of febrile seizures occurring within various time intervals after vaccination in 12- to 60-month-old children who had neither been vaccinated against measles, mumps, rubella, or varicella, nor had a history of the wild-type infections (N=31,298 vaccinated with ProQuad, including 31,043 who were 12 to 23 months old). The incidence of febrile seizures was also assessed in a historical control group of children who had received their first vaccination with M-M-R®II and VARIVAX concomitantly (N=31,298, including 31,019 who were 12 to 23 months old). The secondary objective was to assess the general safety of ProQuad in the 30-day period after vaccination in children 12 months to 12 years old.

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

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

VARIVAX® (Varicella Virus Vaccine Live) is a vaccine indicated for active immunization for the prevention of varicella in individuals 12 months of age or older.

M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live) is indicated for simultaneous vaccination against measles, mumps, and rubella in individuals 12 months of age or older.

Selected Safety Information for ProQuad

Contraindications: ProQuad, M-M-R®II, and VARIVAX are contraindicated in certain individuals, including those with: primary or acquired immunodeficiency conditions including AIDS; family history of congenital or hereditary immunodeficiency or receiving immunosuppressive therapy; blood dyscrasias; thrombocytopenia; untreated tuberculosis; leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems; an active febrile illness or infection.

Hypersensitivity: ProQuad, M-M-R®II, and VARIVAX are contraindicated in patients with a history of hypersensitivity to any component of the vaccine (gelatin). Children with anaphylaxis or immediate hypersensitivity to eggs may be vaccinated with ProQuad and M-M-R®II with extreme caution and adequate treatment should be readily available should a reaction occur.

Neomycin Precautions: For patients vaccinated with ProQuad and M-M-R®II neomycin allergies most commonly manifest as contact dermatitis, which is not a contraindication to receiving either vaccine. VARIVAX is contraindicated in patients who have a neomycin allergy.

Pregnancy Precautions: ProQuad, M-M-R®II, and VARIVAX are contraindicated for use in pregnant women. If vaccination of postpubertal females is undertaken pregnancy should be avoided for 3 months following vaccination. VARIVAX is a live, attenuated varicella virus, and it is known that wild-type varicella virus, if acquired during pregnancy, can cause congenital varicella.

Febrile Seizures: 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 and VARIVAX administered separately.

Cerebral Injury/Seizures: Use caution when administering ProQuad and M-M-R®II to children with: a history of cerebral injury or seizures or any other condition in which stress due to fever should be avoided.

Varicella Transmission and Precautions: Advise patients administered ProQuad or VARIVAX to avoid: close contact with high-risk individuals susceptible to varicella for up to 6 weeks following vaccination since transmission of varicella vaccine virus to susceptible contacts has been reported.

Immune Globulins and Transfusions: For ProQuad and M-M-R®II defer vaccination for at least 3 months following blood or plasma transfusions, or administration of immune globulins (IG). For VARIVAX, defer vaccination for ≥5 months following blood or plasma transfusions or administration of immune globulins. 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.

Use of Salicylates: Advise patients vaccinated with ProQuad or VARIVAX to avoid use of salicylates for 6 weeks following vaccine administration.

Vaccine-related Adverse Events: The following have been reported for ProQuad, M-M-R®II, and VARIVAX: injection-site reactions (pain/tenderness/soreness, erythema, and swelling); irritability; and rash on the body or at the injection site. 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.

VARIVAX Dose-related Adverse Events: In a clinical trial involving children who received 2 doses of VARIVAX® 3 months apart, the incidence of injection-site clinical complaints 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%).

Concomitant Vaccines With ProQuad: ProQuad may be administered concomitantly with Haemophilus influenzae type b conjugate (meningococcal protein conjugate) and hepatitis B (recombinant) vaccine. It may also be administered concomitantly with pneumococcal 7-valent conjugate vaccine and/or hepatitis A vaccine (inactivated) at separate injection sites. There are insufficient data to support concomitant vaccinations with the diphtheria, tetanus, and acellular pertussis vaccine adsorbed and no data regarding the administration of ProQuad with inactivated poliovirus vaccine or with other live virus vaccines.

Tuberculin Testing: If a tuberculin test is to be done with M-M-R®II and ProQuad, it should be administered either any time before, simultaneously with, or at least 4 to 6 weeks after vaccination. With VARIVAX, tuberculin testing may be performed before the vaccine is administered or at least 4 weeks following vaccination.

Additional ProQuad Precautions: No clinical data are available regarding the development or worsening of thrombocytopenia in individuals vaccinated with ProQuad. The safety and efficacy of ProQuad for use in children known to be infected with human immunodeficiency viruses and after exposure to measles, mumps, rubella, or varicella have not been established.

Additional M-M-R®II Precautions: Additional adverse reactions, which have been reported without regard to causality, include, febrile convulsions, arthritis, thrombocytopenia, encephalitis and encephalopathy in their diverse clinical presentations.

Additional VARIVAX Precautions: There are insufficient data to assess the rate of protection of VARIVAX against the serious complications of chickenpox in adults (eg, encephalitis, hepatitis, pneumonia), during pregnancy. It is also not known if varicella vaccine virus is excreted in human milk. A boost in antibody levels has been observed in vaccinees following exposure to wild-type varicella, which could account for the apparent long-term persistence of antibody levels in studies. The duration of protection from varicella infection after vaccination is unknown.

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

Dosage And Administration for ProQuad
ProQuad:

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.

VARIVAX:

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.

M-M-R®II:

The dose for any age is 0.5 mL administered subcutaneously.

The recommended age for primary vaccination is 12 to 15 months and the second dose should be given at 4 to 6 years of age.

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

US-QDX-00096 09/19