Ask the Experts: Combination Vaccines

Results (42)

Combination vaccines can be used for children who have fallen behind. Combination vaccines may be used when any of the components are indicated and none are contraindicated. The minimum interval between doses is the greatest interval between any of the individual antigens. For example, the minimum interval between the first and second doses of MMR is 4 weeks and the minimum interval between the first and second doses of varicella vaccine is 12 weeks. When the two vaccines are combined in MMRV (ProQuad, Merck) the minimum interval between MMRV dose #1 and dose #2 is 12 weeks, which is the greatest of the minimum intervals of the two vaccines if given separately.

Last reviewed: July 15, 2023


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Last reviewed: May 9, 2023

Switching between combination and single-antigen vaccines poses no problem if you maintain the recommended minimum intervals for all vaccines and the vaccines are licensed for the age of the patient.

Last reviewed: July 15, 2023

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, since trade names could be misinterpreted or discontinued.

Last reviewed: July 15, 2023

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.

Last reviewed: July 15, 2023

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., DTaP-IPV-HepB or DTaP-IPV/Hib). There is a combined VIS (the multi-vaccine VIS) that can substitute for any or all of the routine vaccines given from birth–6 months (DTaP, IPV, Hib, PCV and HepB vaccines). VISs in English and many other languages are available at www.immunize.org/vis/.

Last reviewed: July 15, 2023

Pediarix contains the vaccine components DTaP, IPV, and HepB. The primary series is 3 doses (0.5 mL) given intramuscularly at 2, 4, and 6 months of age. Pediarix is licensed by the Food and Drug Administration (FDA) for only the first 3 doses of the DTaP series. It should not be given to infants younger than 6 weeks of age or to children 7 years or older.

Last reviewed: July 15, 2023

Yes, although the package inserts states that Pediarix should only be given to infants born to mothers who are HBsAg-negative, ACIP voted in 2003 to expand its recommendations for use to include infants born to women whose HBsAg status is positive or unknown beginning no earlier than age 6 weeks.

Last reviewed: July 15, 2023

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. Pediarix may only be used in children younger than age 7 years.

Last reviewed: July 15, 2023

No. Pediarix is licensed for doses 1, 2, and 3 of the DTaP primary series through age 6 years.

Last reviewed: July 15, 2023

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.

Last reviewed: July 15, 2023

FDA licensed Pentacel in 2008 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 through 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 the chance of giving one component of the vaccine without the other. The DTaP-IPV component should never be administered alone.

Last reviewed: July 15, 2023

Yes, as long as minimum intervals between doses are maintained.

Last reviewed: July 15, 2023

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. The DTaP-IPV component will count as valid doses of DTaP and IPV vaccines, but take measures to prevent this error in the future. 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 saline diluent. If you have a vial of lyophilized ActHib but neither diluent, you must contact the manufacturer (Sanofi) and obtain ActHib diluent.

Last reviewed: July 15, 2023

While administration of Pentacel to a 5-year-old would be considered off-label and a vaccine administration error, the doses of DTaP and IPV can be counted as valid and do not need to be repeated. Hib vaccine is not routinely administered after a child has reached the age of 5 years so it is also a vaccine administration error. You should explain this error to the parents and assure them that the extra Hib dose will cause no harm.

Last reviewed: July 15, 2023

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.

Last reviewed: July 15, 2023

Yes. In 2009 ACIP updated its recommendations for use of IPV, partly in response to the availability of newer combination vaccines (e.g., Pentacel) that include an IPV component. The change did not apply to children who had already completed an acceptable 4-dose series of IPV before the updated schedule was published in August 2009. Since August 2009, ACIP has recommended 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. 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 current polio vaccine recommendations, go to the ACIP recommendations website at www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/polio.html.

Last reviewed: July 15, 2023

Pentacel (DTaP-IPV/Hib) inadvertently administered to children six years of age and older is considered a vaccine administration error. However, none of the vaccine components need to be repeated.

Last reviewed: July 15, 2023

In 2018, FDA licensed Vaxelis for use in children age 6 weeks through 4 years: it is indicated as a 3-dose series for infants at ages 2, 4, and 6 months. ACIP voted to add Vaxelis to the Vaccines for Children (VFC) Program in 2019.

The MSP Vaccine Company was created as a joint venture between Merck and Sanofi Pasteur to produce Vaxelis. Vaxelis contains the same DTaP components as Pentacel (Sanofi Pasteur). The IPV component is the same as IPOL (Sanofi Pasteur). The Hib component is the same as PedvaxHIB (Merck), but in a decreased amount. The HepB component is the same as the pediatric formulation of Recombivax HB (Merck), but in an increased amount. Vaxelis is a liquid vaccine that does not require reconstitution.

The complete recommendations for the use of Vaxelis are available at: www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6905a5-H.pdf.

Last reviewed: July 15, 2023

Yes. Vaxelis may be used for children younger than age 5 years requiring a catch-up primary series, using appropriate minimum intervals. It is not approved as the booster dose of DTaP [dose 4 or 5] or IPV [dose 4] or Hib [dose 4]. If Vaxelis is inadvertently given as a booster dose, it may count as valid and does not need to be repeated.

Last reviewed: July 15, 2023

Historically, AI/AN infants were more likely than other U.S.-born infants to develop Hib meningitis before being old enough to complete a primary series of Hib-containing vaccine. ACIP prefers that AI/AN infants be vaccinated with PedvaxHIB because it can stimulate protective levels of antibodies after the first dose.

Vaxelis contains the same Hib vaccine components as PedvaxHIB, but in smaller quantities. At the time ACIP approved Vaxelis, no data were available on the immune response to the Hib component of Vaxelis after the first dose, so ACIP did not make a preferential recommendation for Vaxelis in AI/AN infants. ACIP stated it would re-evaluate its decision if new information becomes available.

Last reviewed: July 15, 2023

Fever after vaccination was more common, reported in almost half of infants, compared to about one-third of infants who received Pentacel (DTaP-IPV/Hib). However, the rates of fever-related medical visits or febrile seizures were similar in both groups.

Last reviewed: July 15, 2023

In 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.

Last reviewed: July 15, 2023

Quadracel (Sanofi) is a combination DTaP and IPV vaccine. It was approved by the FDA in 2015 for use in children 4 through 6 years of age as the fifth dose in the DTaP series, and as the fourth or fifth dose in the IPV series in children who have received 4 doses of Pentacel (DTaP-IPV-Hib, Sanofi) and/or Daptacel (DTaP, Sanofi) vaccine. It should not be given to children younger than age 4 years. CDC published a short MMWR article about Quadracel on September 4, 2015 (www.cdc.gov/mmwr/pdf/wk/mm6434.pdf, pages 948–9).

Last reviewed: July 15, 2023

Yes. Although it is preferable to use the same manufacturer’s DTaP vaccine for all of the doses in the series, you can give either Kinrix or Quadracel 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 or Quadracel is the only product stocked.

Last reviewed: July 15, 2023

Use of either Kinrix (GSK) or Quadracel (Sanofi) in a child younger than age 4 years 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. Both the DTaP and IPV will need to be repeated after the child’s fourth birthday.

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.

Last reviewed: July 15, 2023

Since both Kinrix and Quadracel are licensed and recommended only for children ages 4 through 6 years, you should take measures to prevent this error in the future. However, you can count this as a valid dose for 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).

Last reviewed: July 15, 2023

Kinrix (GSK) and Quadracel (Sanofi) brands of combination DTaP-IPV vaccine are 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.

Last reviewed: July 15, 2023

Both brands of DTaP-IPV pediatric combination vaccines (Kinrix, GSK; Quadracel, Sanofi) are only licensed for use as the fifth dose of the DTaP vaccine series and the fourth (or fifth, for Quadracel) dose of the IPV series in children age 4 through 6 years. CDC has provided this guidance for when Kinrix or Quadracel are given off-label:

  • Kinrix or Quadracel given to a child younger than 4 years as DTaP and IPV doses 1, 2, or 3: Count as valid if all minimum intervals met.
  • Kinrix or Quadracel given to a child younger than 4 years as DTaP and IPV doses #4 and/or #5: Count as valid for DTaP #4; not valid for DTaP #5 or IPV #4, both of which must be administered at age 4 through 6 years.

However, you should check with your state immunization program to see what they will accept. Checking with your state is particularly important for validating a last dose of IPV vaccine administered before the fourth birthday. Their guidance may vary depending on the date of administration or your upcoming travel plans. Contact information can be found here: www.immunize.org/coordinators.

Last reviewed: July 15, 2023

Twinrix 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, people with chronic liver disease, men who have sex with men, illegal drug users, or to people who simply want to be immune to both diseases. A Twinrix series consists of 3 doses given intramuscularly on a 0, 1, and 6 month schedule.

Last reviewed: July 15, 2023

Minimum intervals for Twinrix are 4 weeks between dose #1 and dose #2, and 5 months between dose #2 and dose #3.

Last reviewed: July 15, 2023

Yes. This was a vaccine administration error since Twinrix, a combination hepatitis A/hepatitis B vaccine, is not licensed for people younger than 18. However, the hepatitis A and hepatitis B components can be counted as valid doses. The third dose of the Twinrix series should be given at least five months after the second dose.

Last reviewed: July 15, 2023

Twinrix is normally given as a 3-dose series on a schedule 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 fourth (booster) dose at least 12 months after the first dose.

Last reviewed: July 15, 2023

Twinrix is licensed as a 3-dose series for people age 18 years and older (minimum interval between dose 1 and dose 2 is 4 weeks; minimum interval between dose 2 and dose 3 is 5 months). It is also approved for use in an accelerated 4-dose schedule in adults, with doses given at 0, 7, and 21-30 days, followed by a booster dose at 12 months. There is no accelerated schedule for single antigen HepA or HepB vaccines, so the recommendations below presume the use of the Twinrix 3-dose routine schedule, with a minimum interval between dose 1 and dose 2 of 4 weeks.

If Twinrix is not available or if you choose not to use Twinrix to complete the hepatitis A (HepA) and hepatitis B (HepB) series, you should do the following:

  • If 1 dose of Twinrix was given, complete the series with 2 adult doses of HepA and 2 adult doses of HepB.
  • If 2 doses of Twinrix were given, complete the schedule with 1 adult dose of HepA and 1 adult dose of HepB.

Another way to consider this is as follows:

  • A dose of Twinrix contains a standard adult dose of HepB and a pediatric dose of HepA. So, a dose of Twinrix can be substituted for any dose of the HepB series but not for any dose of the HepA series.
  • Any combination of 3 doses of adult HepB or 3 doses of Twinrix is a complete series of HepB vaccine
  • One dose of Twinrix and 2 doses of adult HepA is a complete series of HepA
  • Two doses of Twinrix and 1 dose of adult HepA is a complete series of HepA
Last reviewed: June 3, 2024

No. Twinrix contains 50% less hepatitis A antigen component than Havrix, GSK’s monovalent HepA vaccine [720 vs. 1440 EL.U.], so the patient would not receive the recommended dose of HepA vaccine antigen.

Last reviewed: July 15, 2023

ProQuad was licensed in 2005 for use in children ages 12 months through 12 years. It combines the measles-mumps-rubella (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.merck.com/product/usa/pi_circulars/p/proquad/proquad_pi_4171.pdf.

Last reviewed: July 15, 2023

Post-licensure studies of MMRV suggested that, during the 5–12 days after vaccination, 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.

For this reason, the recommendations for use of MMRV vaccine are as follows:

  • The routinely recommended ages for measles, mumps, rubella, and varicella vaccination are 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 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, if available, over separate injections of its equivalent component vaccines (i.e., MMR vaccine and varicella vaccine).
  • A personal or family (e.g., 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.

Last reviewed: July 15, 2023

Absolutely not. Vaccines should never be mixed except when specifically approved by FDA and packaged for that specific purpose.

Last reviewed: July 15, 2023

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.

Last reviewed: July 15, 2023

In the case of an expired live vaccine, the issue is not necessarily the routine minimum interval (three months in the case of varicella and ProQuad vaccines), but the interval that would prevent viral interference if the expired vaccine happened to be still viable. This interval is considered to be four weeks (28 days). The repeat dose should be administered four weeks after the expired dose.

Last reviewed: July 15, 2023


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Last reviewed: May 23, 2023

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.

Last reviewed: July 15, 2023

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