| Combination Vaccines |
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| General Issues |
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Can combination vaccines be used with children
who have fallen behind with their
vaccinations? If so, what schedule should we
follow? |
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| 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. |
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| Can we switch
back and forth from separate vaccines at one
visit to combination vaccines at another
visit? For example, if a child is given
separate DTaP, IPV, Hib, and HepB vaccines
during her 2-month visit, could we give her
either DTaP-IPV/Hib (Pentacel) or DTaP-HepB-IPV
(Pediarix) at her 4-month visit? |
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| Switching between
combination and single-antigen vaccines poses
no problem as long as you maintain the
recommended minimum intervals for all vaccines
and the vaccines are licensed for the age of
the patient. |
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| How should we
record combination vaccines on paper records
(e.g., parent-maintained records,
non-computerized office systems)? |
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| 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. |
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| Why does the
nomenclature for combination vaccines contain
either hyphens or, sometimes, a forward slash? |
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| 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. |
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| How can we
obtain a VIS for combination vaccines? |
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| 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 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/. |
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| What is the
dosing schedule for Pediarix? |
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| 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. |
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| Can Pediarix
be given to infants born to mothers who are
HBsAg-positive? |
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| 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. |
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| Can Pediarix
be used in infants and children who have
fallen behind? |
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| 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. |
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| Our nurses
have been routinely giving Pediarix 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? |
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| No. Pediarix is
licensed for doses 1, 2, and 3 of the DTaP
primary series through age 6 years. |
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| We have been
giving Pediarix to children who are overdue
for DTaP #4, IPV #3, and HepB #3. Is this an acceptable practice? |
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| 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. |
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| Please
describe the combination vaccine DTaP-IPV/Hib
(Pentacel) and how it should be used. |
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| 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. |
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| Can we give
Pentacel to a child who has previously
received separate injections of one or more of
these antigens? |
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| Yes, as long as
minimum intervals between doses are
maintained. |
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| A 5-year-old
patient received Pentacel (DTaP-IPV/Hib) for
the 5th dose of DTaP instead of Quadracel
(DTaP-IPV). Can I count the Pentacel as a
valid
dose or will we need to revaccinate this
patient? |
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| 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. |
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| We
inadvertently gave a child only the DTaP-IPV
component of Pentacel 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? |
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| 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 ActHib but neither
diluent, you must contact the manufacturer
(Sanofi Pasteur) and obtain ActHib diluent. |
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| Can we give
Pentacel if we don't know the type of DTaP
vaccine the child previously received? |
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| 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. |
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| When we give
the combination Pentacel 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
inactivated polio vaccine (IPV). Does the
child still need a booster dose of IPV before
entering kindergarten? |
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| 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
www.cdc.gov/mmwr/preview/mmwrhtml/mm5830a3.htm. |
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| Although
licensed by the Food and Drug Administration
for use through age 4 years, a dose of
Pentacel was inadvertently given to a
six-year-old. Do any
components of the Pentacel dose need to be
repeated? |
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| 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. |
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| DTaP-IPV-Hib-HepB (Vaxelis, MCM Vaccine Company) |
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| Please tell us
about the combination vaccine DTaP-IPV-Hib-HepB
(Vaxelis, MCM Vaccine Company) and the
recommendations for its use. |
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| 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. |
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| The MCM 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. |
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| The complete
recommendations for the use of Vaxelis are
available at:
www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6905a5-H.pdf. |
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| Can Vaxelis be
used for older children behind on their
immunization schedule? |
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| 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. |
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| PedvaxHIB
(Merck) is the Haemophilus influenzae type b
(Hib) vaccine preferred for American Indian
and Alaskan Native (AI/AN) infants. Since Vaxelis
contains the same kind of Hib vaccine, is it
also preferred? |
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| 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. |
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| 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. |
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| Are there any
side effects of Vaxelis I should know about? |
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| 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. |
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| Vaxelis was
approved by the ACIP in 2019, but I can’t find
it. When will it be available in the United States? |
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| The manufacturer
has stated that it will not become available
in the United States before 2021. |
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| DTaP-IPV (Kinrix, GlaxoSmithKline; Quadracel, Sanofi Pasteur) |
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| Please tell us
about the combination vaccine Kinrix and the
recommendations for its use. |
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| 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. |
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| Can Kinrix be
used at kindergarten entry if the previous
brand of DTaP is unknown? |
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| Yes. Although 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. |
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| 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? |
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| Use of Kinrix 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. |
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| If Kinrix is
inadvertently given to a child age 15 through
18 months, as the fourth DTaP dose and the
third IPV dose, do the DTaP and IPV doses need
to
be repeated? |
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| Since Kinrix is
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). |
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| If an
8-year-old child who needed IPV and Td
vaccines was mistakenly given a dose of Kinrix.
Does the Kinrix count as a valid dose of polio
and Td
vaccine? |
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| 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. |
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| A dose of
Kinrix was inadvertently given to a
4-month-old in our practice who needed DTaP
and IPV. Can this dose be considered valid? |
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| Kinrix is only
licensed for use as the fifth dose of the DTaP
vaccine series and the fourth dose of the IPV
series in children age 4 through 6 years. CDC
has provided this guidance for when Kinrix is
given off-label: |
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Kinrix 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. |
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Kinrix 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. |
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| 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. |
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| Please provide
information about Quadracel and
recommendations for its use. |
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| Quadracel (Sanofi
Pasteur) 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
Pasteur) and/or Daptacel (DTaP, Sanofi Pasteur) 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). |
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| Can Quadracel
be used to complete a series with vaccines
other than Daptacel or Pentacel? |
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| ACIP recommends
the same brand of DTaP be used for all doses
but that a different brand can be used if necessary. So Quadracel can be used in a
series with another brand of DTaP if
necessary. |
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| I would like
more information about Twinrix, the
combination hepatitis A and B vaccine. |
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| 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. |
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| What are the
minimum intervals for the 3-dose series of
Twinrix? |
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| Minimum intervals
for Twinrix are 4 weeks between dose #1 and
dose #2, and 5 months between dose #2 and dose
#3. |
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| A 17-year-old
received two doses of Twinrix, separated by
one month. The second dose was six months ago and she is now 18 years old. Can she receive
the third dose of Twinrix to complete the
series? |
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| 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. |
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| We heard that
there is an alternative schedule for the
Twinrix that gives the patient protection
sooner than the standard schedule does. Can
you tell us
more? |
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| 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 dose at 12 months. |
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| 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? |
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| 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
hepatitis A and hepatitis B series, you should
do the following: |
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If 1 dose of Twinrix was given,
complete the series with 2 adult doses
of hepatitis A vaccine and 2 adult
doses of hepatitis B vaccine. |
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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. |
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| Another way to
consider this is as follows: |
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A dose of Twinrix contains a standard
adult dose of hepatitis B vaccine and
a pediatric dose of hepatitis A vaccine. So 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. |
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Any combination of 3 doses of adult
hepatitis B or 3 doses of Twinrix is a
complete series of hepatitis B vaccine |
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One dose
of Twinrix and 2 doses of adult
hepatitis A is a complete series of
hepatitis A vaccine |
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Two doses
of Twinrix and 1 dose of adult
hepatitis A is a complete series of
hepatitis A vaccine |
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| 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? |
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| 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. |
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| How should
MMRV be used? |
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| ProQuad was
licensed in 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.merck.com/product/usa/pi_circulars/p/proquad/proquad_pi_4171.pdf. |
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| Please review
the specifics of CDC recommendations for the
use of the MMRV. |
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| 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. |
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For this reason,
the recommendations for use of MMRV vaccine
are as follows:
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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. |
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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. |
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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). |
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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. |
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The complete
recommendations for the use of MMRV vaccine
are available on CDC's website at
www.cdc.gov/mmwr/pdf/rr/rr5903.pdf. |
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| 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? |
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| Absolutely not.
Vaccines should never be mixed except when
specifically approved by FDA and packaged for
that specific purpose. |
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| 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, what is the spacing requirement between
the two doses? |
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| 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. |
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| MMRV was
mistakenly given to a 31-year-old instead of
MMR. Can this be considered a valid dose? |
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| 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. |
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| An expired
dose of ProQuad (MMRV, Merck) was given to a
patient. We assume that the repeat dose should
be given in three months because the
spacing between doses of a combination vaccine
depends on the longest minimum interval of a
component (in this case the varicella vaccine
component).
Is this correct? |
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| 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. |
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ACIP Recommendations
Vaccine Information Statements 
