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Combination Vaccines

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Combination Vaccines
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HepA-HepB (Twinrix®)
Hib-HepB (Comvax®)
DTaP-IPV-HepB (Pediarix®) DTaP-IPV (Kinrix®) MMR-Var (ProQuad®)
DTaP-IPV/Hib (Pentacel®)
General Issues
Can combination vaccines be used with children who have fallen behind with their vaccinations? If so, what schedule should we follow?
Combination vaccines can be used for children who have fallen behind. In this case, the minimum intervals between doses would be the greatest interval between any of the individual antigens. For example, the minimum interval between Hib dose #2 and Hib dose #3 is 4 weeks and the minimum interval between HepB dose #2 and HepB dose #3 is 8 weeks. When the two antigens are combined, as in Comvax, the minimum interval between Comvax dose #2 and Comvax dose #3 would be 8 weeks, which is the greatest of the minimum intervals of the two vaccines if given separately. Likewise, the minimum age for the 3rd dose of Comvax is the oldest minimum age of the two antigens (i.e., age 24 weeks).
Can we switch back and forth from monovalent vaccines at one visit to combination vaccines at another visit? For example, if a child is given monovalent DTaP, IPV, Hib, and Hep B during her 2-month visit, could we give her either DTaP-IPV/Hib (Pentacel) or DTaP-HepB-IPV (Pediarix) at her 4-month visit?
Switching between combination and single-antigen vaccines poses no problem as long as you maintain the recommended minimum intervals for all vaccines.
How should we record combination vaccines on paper records (e.g., parent-maintained records, non-computerized office systems)?
You should record the generic abbreviation for the type of vaccine given (e.g., DTaP-IPV-HepB) in each of the sections that correspond to the separate antigens listed on the record (e.g., DTaP section, polio section, hepatitis B section). If possible, avoid using trade names (who remembers which antigens were in Acel-Imune?).
Why does the nomenclature for combination vaccines contain either hyphens or, sometimes, a forward slash?
The hyphen (-) is intended to indicate that the antigens are mixed together by the manufacturer before the product is sold and the forward slash (/) indicates that the two products are to be reconstituted by the user.
How can we obtain a VIS for combination vaccines?
With some exceptions, there aren't VISs for combination vaccines. Instead, providers should provide a separate VIS for each vaccine component in the combination (e.g., HepB-Hib, or DTaP-IPV-HepB). The exceptions are for DTaP, Tdap, Td, and MMR vaccines, which all have a VIS that covers all separate components of the vaccine, and a combined VIS that can substitute for any or all of the routine vaccines given from birth-6 months (DTaP, IPV, Hib, PCV, hepatitis B, and rotavirus vaccines).
DTaP-IPV-HepB (Pediarix by GlaxoSmithKline) Back to top
What is the dosing schedule for the DTaP-IPV-HepB combination vaccine (Pediarix by GSK)?
Pediarix contains the vaccine components DTaP, IPV, and hepatitis B. The primary series is 3 doses (0.5 mL) given intramuscularly at 2, 4, and 6 months of age. It should not be given to infants younger than 6 weeks of age nor to children 7 years or older.
Can Pediarix be given to infants born to mothers who are HBsAg-positive?
Yes, although the package inserts states that Pediarix should only be given to infants born to mothers who are HBsAg-negative, the ACIP voted on February 26, 2003, to expand its recommendations for use to also include infants born to mothers whose HBsAg status is positive or unknown beginning no earlier than age 6 weeks. In expanding the use of Pediarix beyond FDA-prescribing information, ACIP remained consistent with its 1997 vote, which permitted the use of Comvax (Merck's Hib-hepatitis B combination vaccine) to complete the hepatitis B vaccine series in infants born to HBsAg-positive mothers and mothers whose HBsAg status is unknown.
Can Pediarix be used in infants and children who have fallen behind?
Yes. As with any combination vaccine, it may be used when any of the components are indicated and none are contraindicated. Providers must observe spacing intervals such that the minimum interval between doses is equal to the greatest interval of any of the individual antigens. The vaccine may only be used in children younger than age 7 years.
Our nurses have been routinely giving DTaP-HepB-IPV (Pediarix; GSK) to toddlers who were overdue for their third doses of DTaP, IPV, and HepB. Recently someone told me that Pediarix is only intended for use at 2, 4, and 6 months of age. Did we err?
No, you did not err. Pediarix is licensed for use in children ages 6 weeks through 6 years for doses 1, 2, and 3 of the DTaP primary series. This would not constitute a vaccine error, as long as you observe the recommended minimum intervals for all the vaccine components (i.e., DTaP, IPV, and HepB).
We have been giving DTaP-HepB-IPV (Pediarix) to children who are overdue for DTaP #4, IPV #3, and HepB #3. Is this an acceptable practice?
No. Pediarix is intended to be used only for doses 1, 2, or 3 of the DTaP primary series; consequently using Pediarix for DTaP #4 is off-label and not recommended. You should take measures to prevent this error in the future. The DTaP, IPV, and HepB doses given in this scenario do not need to be repeated as long as you met the recommended minimum intervals for each vaccine component (DTaP, IPV, HepB). If you did meet the minimum intervals, the doses should be counted as valid.
DTaP-IPV/Hib (Pentacel by sanofi pasteur) Back to top
Please describe the new combination vaccine Pentacel and how it should be used.
FDA licensed Pentacel on June 20, 2008. It is approved for use as a 4-dose series in infants and children at ages 2, 4, 6, and 15-18 months. It should not be used for any dose in the primary series for children age 5 years or older or as the booster dose for children ages 4-6 years. The DTaP-IPV component is supplied as a sterile liquid, which is used to reconstitute lyophilized (freeze-dried) ActHIB vaccine. The two components of the vaccine should be stored together in the carton to reduce vaccine administration errors. The DTaP-IPV component should never be administered alone.
Can we give Pentacel to a child who has previously received separate injections of one or more of these antigens?
Yes, as long as minimum intervals are maintained.
We inadvertently gave a child only the DTaP-IPV component of Pentacel (DTaP-IPV/Hib; sanofi pasteur), not realizing that this component was intended to reconstitute the Hib component. Does this count as a valid dose of DTaP and IPV? Can we mix the unused Hib component with sterile water and give it separately?
Use of DTaP-IPV solution as the diluent for the Hib component is specifically written both on the Pentacel box AND on the DTaP-IPV vial label. In answer to your first question, the DTaP-IPV component will count as valid doses of DTaP and IPV vaccines, but take measures to prevent this error in the future. In answer to your second question, NO, you cannot mix the Hib component with sterile water. ActHib must ONLY be reconstituted with either the DTaP-IPV solution supplied with Pentacel, or with a specific ActHib diluent. If you have ActHib but neither diluent, you must contact the manufacturer (sanofi pasteur) and obtain ActHib diluent.
Can we give Pentacel if we don't know the type of DTaP vaccine the child previously received?
Yes. CDC recommends that whenever feasible, only one manufacturer's DTaP product be used for the entire pertussis series, but that vaccinations should not be deferred if the DTaP product previously given is unavailable or unknown.
When we give the combination DTaP-IPV/Hib vaccine (Pentacel by sanofi) for the primary series to a child at ages 2, 4, 6, and 15–18 months, the child receives a total of 4 doses of IPV. Does the child still need a booster dose of IPV before entering kindergarten?
Yes. In summer 2009, ACIP updated its recommendations for use of inactivated poliovirus vaccines (IPV), partly in response to the availability of newer combination vaccines (e.g., Pentacel) that include an IPV component. ACIP now recommends that children receive at least 1 dose of IPV at age 4 through 6 years, even if they have previously received 4 doses. The interval between the next-to-last and last dose should be at least 6 months. (Note: This updated recommendation applies to all IPV-containing vaccines, including combination vaccines as well as IPV given as a single product.) This means that some children may receive a total of 5 doses, a practice ACIP considers acceptable. This is similar to the recommendation for the last dose in the DTaP series. To view the updated polio vaccine recommendations, go to www.cdc.gov/mmwr/preview/mmwrhtml/mm5830a3.htm.
DTaP-IPV (Kinrix by GlaxoSmithKline) Back to top
Can Kinrix (DTaP-IPV; GSK) be used at kindergarten entry if the previous brand of DTaP is unknown?
Yes. Though it is preferable to use the same manufacturer's DTaP vaccine for all of the doses in the series, you can give Kinrix as the fifth dose of DTaP and fourth dose of IPV at age 4 through 6 years if the previous brand is unknown or if Kinrix is the only product stocked.
We mistakenly gave Kinrix (DTaP-IPV) to a child age 3 years 10 months. We later realized that he had a prior history of receiving 4 doses of DTaP and IPV. Can the dose of Kinrix count as his 4 through 6 year booster?
Use of the vaccine in a child younger than age 4 is off-label and is not recommended. You should take measures to prevent this error in the future. The minimum age for the fifth dose of the DTaP series is 4 years, and the minimum age for the final dose of IPV is also 4 years, so this dose of Kinrix is not valid. For detailed information, see CDC's useful table "Recommended and Minimum Ages and Intervals Between Doses of Routinely Recommended Vaccines" at www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/A/age-interval-table.pdf.
If Kinrix is inadvertently given to a child age 15 through 18 months, as the fourth DTaP dose and the third IPV dose, does the Kinrix dose have to be repeated?
No, as long as minimum intervals between previous doses have been met. Kinrix is licensed and recommended only for children age 4 through 6 years. You should take measures to prevent this vaccine administration error in the future. However, you can count this as a valid dose for both DTaP and IPV as long as you met the minimum interval between administering dose #3 and dose #4 of DTaP (6 months) and dose #2 and dose #3 of IPV (4 weeks).
Please tell us about the combination vaccine Kinrix and the recommendations for its use.
On June 24, 2008, FDA licensed Kinrix, a combination DTaP and IPV vaccine. It is approved for use as the fifth dose of DTaP and the fourth dose of IPV in children ages 4 through 6 years who received DTaP (Infanrix) and/or DTaP-HepB-IPV (Pediarix) as the first three doses and DTaP (Infanrix) as the fourth dose. It should not be given to children younger than age 4 years.
If an 8-year-old child who needed IPV and Td vaccines was mistakenly given a dose of DTaP-IPV (Kinrix; GSK), will that count as a valid dose of polio and Td vaccine?
Kinrix is licensed and recommended only for use in children ages 4 through 6 years, so you should take measures to prevent this error in the future. However, you can count the IPV dose as valid as long as it has met the minimum interval (4 weeks between doses except for the final dose in the series, which should be 6 months from the previous dose). With regard to the mistaken administration of the DTaP in a child older than age 6 years, the dose can be counted and does not need to be repeated with Td.
HepA-HepB (Twinrix) Back to top
I would like more information about Twinrix, the combination hepatitis A and B vaccine.
Twinrix (GlaxoSmithKline) is an inactivated combination vaccine containing both hepatitis A virus (HAV) and HBV antigens. The vaccine contains 720 EL.U. of hepatitis A antigen (half of the Havrix adult dose) and 20µg of hepatitis B antigen (the full Engerix-B adult dose). In the U.S., Twinrix is licensed for use in people who are age 18 years or older. It can be administered to people who are at risk for both hepatitis A and hepatitis B, such as certain international travelers, men who have sex with men, illegal drug users, or to people who simply want to be immune to both diseases. Primary immunization consists of 3 doses given intramuscularly on a 0, 1, and 6 month schedule. Twinrix cannot be used for postexposure prophylaxis.
We heard that there is an alternative schedule for the adult HepA-HepB (Twinrix; GSK) vaccine that gives the patient protection sooner than the standard schedule does. Can you tell us more?
Yes. Licensed for use in people age 18 and older, the combined HepA-HepB vaccine is normally given as a 3-dose series at intervals of 0, 1, and 6 months. However, if someone needs protection sooner (e.g., imminent foreign travel), you can give it as a 4-dose series at intervals of 0, 7, and 21-30 days, followed by a dose at 12 months.
I have seen adults who have had 1 or 2 doses of Twinrix, but we only carry single-antigen vaccine in our practice. How should we complete their vaccination series with single-antigen vaccines?
Twinrix is licensed as a 3-dose series for people age 18 years and older. If Twinrix is not available or if you choose not to use Twinrix to complete the Twinrix series, you should do the following: If 1 dose of Twinrix was given, complete the series with 2 adult doses of hepatitis B vaccine and 2 adult doses of hepatitis A vaccine. If 2 doses of Twinrix were given, complete the schedule with 1 adult dose of hepatitis A vaccine and 1 adult dose of hepatitis B vaccine.
Another way to consider this is as follows:
A dose of Twinrix contains a standard adult dose of hepatitis B vaccine and a pediatric dose of hepatitis A vaccine. Thus, a dose of Twinrix can be substituted for any dose of the hepatitis B series but not for any dose of the hepatitis A series.
Any combination of 3 doses of adult hepatitis B or 3 doses of Twinrix = a complete series of hepatitis B vaccine
One dose of Twinrix + 2 doses of adult hepatitis A = a complete series of hepatitis A vaccine
Two doses of Twinrix + 1 dose of adult hepatitis A = a complete series of hepatitis A vaccine
We're thinking of using Twinrix and we're wondering whether we can use it for doses #1 and #3 only and use single antigen hepatitis B vaccine for dose #2?
No. Twinrix contains 50% less hepatitis A antigen component than Havrix, GSK's monovalent hepatitis A vaccine [720 vs. 1440 El. U.], so the patient would not receive the recommended dose of hepatitis A vaccine antigen. For this reason, 3 doses of Twinrix must comprise the series.
Hib-HepB (Comvax by Merck) Back to top
A 4-month-old needs both Hib and hepatitis B vaccines today. Can I use Comvax even if the child has not previously received this combination product?
Yes. Comvax can be used when either or both antigens are indicated and neither antigen is contraindicated. Comvax would not be used after the fifth birthday because Hib vaccine is not routinely recommended beyond this age. Comvax should also not be used in infants less than 6 weeks of age.
MMR-Var (ProQuad by Merck) Back to top
How should the combined MMR and varicella vaccine (ProQuad) be used?
ProQuad was licensed in September 2005 for use in children ages 12 months through 12 years. It combines the MMR and varicella vaccines and therefore can be used in place of the individual MMR and varicella vaccines given at ages 12-15 months and 4-6 years. For more information, consult the package insert at www.fda.gov/cber/label/mmrvmer090605LB.pdf
Please review the specifics of the latest CDC recommendations for the use of the combination measles, mumps, rubella, and varicella (MMRV) vaccine.
On May 7, 2010, CDC issued new recommendations for the use of combination MMRV vaccine. Prior to issuing these recommendations, ACIP reviewed results of post-licensure studies that suggest that, during the 5-12 day post-vaccination period, approximately one additional febrile seizure occurred among every 2,600 children ages 12 through 23 months vaccinated with a first dose of MMRV vaccine compared with children in the same age group vaccinated with separate first doses of MMR vaccine and varicella vaccine administered during a single office visit.
The summary of the recommendations for use of MMRV vaccine are as follows:
The routinely recommended ages for measles, mumps, rubella, and varicella vaccination continue to be age 12 through 15 months for the first dose and age 4 through 6 years for the second dose.
  For the first dose of measles, mumps, rubella, and varicella vaccines at age 12 through 47 months, providers may use either measles, mumps, and rubella (MMR) vaccine and varicella vaccine or MMRV vaccine. Providers who are considering administering MMRV vaccine should discuss the benefits and risks of both vaccination options with the parents or caregivers. Unless the parent or caregiver expresses a preference for MMRV vaccine, CDC recommends that providers administer MMR vaccine and varicella vaccine for the first dose in this age group.
  For the second dose of measles, mumps, rubella, and varicella vaccines at any age (15 months through 12 years) and for the first dose at age 48 months and older, use of MMRV vaccine generally is preferred over separate injections of its equivalent component vaccines (i.e., MMR vaccine and varicella vaccine).
  A personal or family (i.e., sibling or parent) history of seizures of any etiology (i.e., cause) is a precaution for MMRV vaccination, and such children generally should be vaccinated with MMR vaccine and varicella vaccine.
The complete recommendations for the use of MMRV vaccine are available on CDC's website at www.cdc.gov/mmwr/pdf/rr/rr5903.pdf
In addition, CDC has issued a new VIS for MMRV, dated 5/21/10, which is available at www.immunize.org/vis and www.cdc.gov/vaccines/pubs/vis/downloads/vis-mmrv.pdf As with all other VISs, it should be given to the parent or vaccine recipient prior to vaccination to facilitate discussion about the vaccine between the patient and provider.
If a 5-year-old child has never received any doses of MMR or varicella vaccine and now the parents want him to catch up with the combination vaccine MMRV (ProQuad; Merck), what is the spacing requirement between the two doses?
Twelve weeks. The spacing between doses of a combination vaccine depends on the longest minimum interval of a component. The minimum interval between doses of MMR is 4 weeks; the minimum interval between doses of varicella vaccine is 12 weeks for a child this age. So you should wait 12 weeks between the doses of MMRV for the two doses to be valid.
MMRV was mistakenly given to a 31-year-old instead of MMR. Can this be considered a valid dose?
Yes, however, this issue is not addressed in the 2010 MMRV ACIP recommendations. Although this is off-label use, CDC recommends that when a dose of MMRV is inadvertently given to a patient age 13 years and older, it may be counted towards completion of the MMR and varicella vaccine series and does not need to be repeated.
If we don't have the combination MMRV vaccine in stock, can I make my own by mixing MMR and Varivax in the same syringe?
Absolutely not. Vaccines should never be mixed except when specifically approved by FDA and packaged for that specific purpose.
This page was reviewed on April 1, 2011
Immunization Action Coalition  •  Saint Paul, MN
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This website is supported in part by a cooperative agreement from the National Center for Immunization and Respiratory Diseases (Grant No. 5U38IP000290) at the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. The website content is the sole responsibility of IAC and does not necessarily represent the official views of CDC.