Vaccine Spotlight
Quadracel: Vaccination Against Diphtheria,
Tetanus, Pertussis, and Poliomyelitis in Children
Juan F. Mosley II, PharmD, CPh, AAHIVP; Lillian L. Smith, PharmD, CPh, MBA;
Crystal K. Parke, PharmD; Jamal A. Brown, PharmD; Justin M. LaFrance, PharmD Candidate;
and Patricia K. Clark, PharmD Candidate
ABSTRACT
Introduction: Vaccinations in school-aged children are
required by state and local law to maintain high vaccination
coverage rates, as well as low rates of vaccine-preventable
diseases. Diphtheria, tetanus, and pertussis are childhood
diseases that can be life threatening; poliomyelitis, another
childhood disease, can be disabling. In turn, vaccinations
were developed to provide protection against these diseases.
Today, several vaccinations are recommended for children,
including but not limited to diphtheria, tetanus, and pertussis
(DTaP) and poliomyelitis (IPV). DTaP requires five doses, and
IPV requires four. Quadracel (diphtheria and tetanus toxoids
and acellular pertussis adsorbed and inactivated poliovirus
vaccine, Sanofi Pasteur Inc.) is a new vaccination developed
to condense the last dose of both DTaP and IPV so they do not
have to be given separately, thus reducing the total number
of vaccinations required.
Discussion: The Quadracel vaccine is an option for use
in children who are completing the DTaP and IPV series. In
a randomized, controlled, phase 3, pivotal trial, Quadracel
proved to be as efficacious and safe as Daptacel (diphtheria
and tetanus toxoids and acellular pertussis vaccine adsorbed,
Sanofi Pasteur Inc.) and IPOL (poliovirus vaccine inactivated,
Sanofi Pasteur Inc.), given separately, to children between the
ages of 4 and 6 years.
Conclusion: Quadracel should be recommended to parents
who have children between the ages of 4 and 6 years who meet
the necessary administration criteria and need to finalize their
DTaP and IPV series. Quadracel’s administration in the vaccination series replaces one additional injection, which may
benefit children who are afraid of receiving shots and parents
who need to schedule one less doctor’s appointment.
Keywords: Quadracel, vaccine, Pentacel, Daptacel, DTaP,
IPOL, IPV
INTRODUCTION
Vaccinations in school-aged children are required by state
and local law to maintain high vaccination coverage rates, as
well as low rates of vaccine-preventable diseases.1 Vaccinations
within the United States have become controversial among
parents who do not want to have their children vaccinated due
to concerns that vaccinations are harmful to their children’s
Drs. Mosley, Smith, Parke, and Brown are Assistant Professors of
Pharmacy Practice at the Florida Agricultural and Mechanical
University, College of Pharmacy and Pharmaceutical Sciences, in
Tallahassee, Florida. Justin LaFrance and Patricia Clark are Doctor
of Pharmacy candidates at that institution.
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health and well-being. Many myths have led some parents to
believe that vaccines can in turn cause autism because of the
chemical thimerosal, a mercury-based preservative, within the
vaccines.2 Although some diseases are not as prevalent as they
were 60 years ago, this should not influence the decision to
vaccinate children or suggest that vaccines are unnecessary.
As a result of the development of vaccines, diseases such as
smallpox have been completely eradicated.
Before vaccinations, measles was a common disease in the
United States. Once a vaccine was developed, the documented
number of measles cases decreased by more than 99%, thus
making it a rare disease.3 However, measles still exists around
the world. To this day, the disease is not completely eradicated, even within the United States. For example, in 2015,
189 people from 24 states and the District of Columbia were
reported to have measles, and the majority of those people
were unvaccinated.4
Diphtheria, tetanus, and pertussis are childhood diseases
that can be life threatening; poliomyelitis, another childhood
disease, can be disabling. Diphtheria, tetanus, and pertussis
are caused not only by bacteria, but by the toxins they produce.
Because of the severity of these infections and their potential to
cause mortality, the diphtheria, tetanus, and pertussis (DTaP)
vaccine was created to prevent both children and adults from
infection by these diseases. Poliovirus causes poliomyelitis,
a disease that attacks the nervous system, causing irreversible paralysis. In turn, the inactivated poliovirus vaccination
(IPV) series was developed for prevention of this debilitating
disease.5,6
Several vaccinations are needed for children to provide
coverage against diseases such as these. More specifically,
five doses of vaccine are required for DTaP, and four doses
are needed for IPV. Quadracel (diphtheria and tetanus toxoids
and acellular pertussis adsorbed and inactivated poliovirus
vaccine, Sanofi Pasteur Inc.) is a new vaccination developed
to condense the last dose of both DTaP and IPV so that the
two scheduled doses do not have to be given separately, thus
reducing the total number of vaccinations required.5,6
INDICATION AND USAGE
Quadracel is a vaccine indicated for the active immunization
of diphtheria, tetanus, pertussis, and poliomyelitis. It is approved
by the Food and Drug Administration for use in children ages
4 to 6 years as a fifth dose for the DTaP vaccination series
and as a fourth or fifth dose in the IPV series in children who
have already received four doses of Pentacel (diphtheria and
Disclosure: The authors report no commercial or financial interests
in regard to this article.
Vaccine Spotlight: Quadracel
Table 1 Pediatric Vaccination Schedule7
Vaccine
Age at
1st Dose
Age at
2nd Dose
Age at
3rd Dose
Age at
4th Dose
Age at
5th Dose
DTaP
2 months
4 months
6 months
15 to 18
months
*4 to 6
years
IPOL
2 months
4 months
6 to 18
months
*4 to 6
years
Poliomyelitis
There are three serotypes of polioviruses, types 1, 2, and
3, which are called enteroviruses. The presence of poliovirus
type-specific neutralizing antibodies has been correlated
with protection against poliomyelitis.5
PIVOTAL CLINICAL TRIAL
Study Overview
A randomized, multicenter, controlled, phase 3 study
was designed to compare the safety and immunogenicity of
the Quadracel vaccine with the Daptacel (DTaP) and IPOL
* Quadracel would be considered as the fifth dose of the DTaP vaccination series as
well as the fourth dose of the IPOL vaccination series.7
(poliovirus vaccine inactivated, Sanofi Pasteur Inc.) vaccines
in children 4 through 6 years of age who were previously
tetanus toxoids and acellular pertussis adsorbed, inactivated
vaccinated with Daptacel and/or Pentacel. This study enrolled
poliovirus and haemophilus b conjugate, Sanofi Pasteur Inc.)
a total of 3,372 participants, who were randomized and vacciand/or Daptacel (diphtheria and tetanus toxoids and acellular
nated at 70 clinical sites in the United States and Puerto Rico.9
5
pertussis vaccine adsorbed, Sanofi Pasteur Inc.). The recomResults were collected by comparing booster response rates
mended schedule of vaccination appears in Table 1.
of diphtheria, pertussis, and tetanus, as well as geometric
mean concentration (GMC) and measured ELISA, following
VACCINE INGREDIENTS
Quadracel administration to subjects vaccinated with Daptacel
Active Ingredients
and IPOL as a fifth dose. Inactivated poliovirus vaccine booster
Each 0.5-mL vial contains 15 limit of flocculation (Lf) diphresponse rates were also compared and measured by neutraltheria toxoid, 5 Lf tetanus toxoid, acellular pertussis antigens
izing assay following Quadracel administration to subjects
(20 mcg detoxified pertussis toxin, 20 mcg filamentous 164
vaccinated with Daptacel and IPOL, as well as the polio (types
hemagglutinin, 3 mcg pertactin, 5 mcg fimbriae types 2 and 3),
1, 2, and 3) geometric mean titer.9
and inactivated polioviruses (40 D-antigen units [DU] type-1
A safety assessment was conducted when Quadracel was
[Mahoney], 8 DU type-2 [MEF-1], 166 32 DU type-3 [Saukett]).5
administered as a fifth dose booster vaccine in participants
who were previously vaccinated with Daptacel and Pentacel
vaccines.9
Inactive Ingredients
The diphtheria, tetanus, and pertussis antigens are combined
with aluminum phosphate, 2-phenoxyethanol, and water for
Results
injection.5
Antibody levels of diphtheria, tetanus, pertussis, and poliovirus antigens were measured in sera prior to vaccination and
CLINICAL PHARMACOLOGY
28 days after vaccination. Results compared the GMC and ELISA
Mechanism of Action
of pertussis, diphtheria, and tetanus between Quadracel and
Diphtheria
Daptacel and IPOL after administration. Quadracel was shown
This acute toxin-mediated disease is caused by toxigenic
to be noninferior to Daptacel and IPOL vaccines administered
strains of Corynebacterium diphtheria. Protection against this
concomitantly at separate sites. In addition, a safety assessment
disease is due to the development of neutralizing antibodies in
was conducted showing that Quadracel had similar safety
diphtheria toxin. A serum diphtheria antitoxin level of at least
immunogenicity profiles as compared to separately adminis0.01 IU/mL is generally regarded as protective and has been
associated with long-term protection.5
Table 2 Booster Response Rates5
DTap = diphtheria, tetanus, pertussis; IPOL = inactivated poliovirus.
Tetanus
This acute disease is caused by an extremely potent neurotoxin produced by the organism Clostridium tetani; protection
against this disease is due to the development of neutralizing
antibodies in tetanus toxin. A serum antitoxin level of at least
0.01 IU/mL, measured by neutralization assay, is considered
minimal protection level, but 0.01 IU/mL or more of Quadracel,
measured by the enzyme-like immunosorbent assay (ELISA)
in clinical studies, is considered protective.5
Pertussis
Known as whooping cough, pertussis is a respiratory disease
caused by the organism Bordetella pertussis. This gram-negative
coccobacillus produces a variety of biologically active components, though their role in either the pathogenesis of or
immunity to pertussis has not been clearly defined.5
Quadracel
(%)
Daptacel + IPOL
(%)
97.3
90.7
100.0
99.6
18.6
99.2
83.1
99.6
99.6
15.5
84.2
91.7
100.0
98.9
6.4
84.3
89.1
99.2
96.8
5.5
Anti-Diphtheria
Booster response
Pre-vaccination % ≥ 0.1 IU/mL
Post-vaccination % ≥ 0.1 IU/mL
Post-vaccination % ≥ 1.0 IU/mL
Post-vaccination GMC (IU/mL)
Anti-Tetanus
Booster response
Pre-vaccination % ≥ 0.1 IU/mL
Post-vaccination % ≥ 0.1 IU/mL
Post-vaccination % ≥ 1.0 IU/mL
Post-vaccination GMC (IU/mL)
IPOL = poliovirus vaccine inactivated; GMC = geometric mean concentration.
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Vaccine Spotlight: Quadracel
Table 3 Common Side Effects Associated With Quadracel5
Clinically Significant
Pain at injection site
> 75%
Increased arm circumference
> 65%
Erythema
> 55%
Swelling
> 40%
Common Systemic Reactions
Myalgia
> 50%
Malaise
> 35%
Headaches
> 15%
tered Daptacel and IPOL vaccines.5,9 Booster response rates for
both Quadracel and Daptacel plus IPOL are shown in Table 2.
ADVERSE EFFECTS
The most common side effects associated with Quadracel
are reported in at least 1% of children seven days after receiving this vaccine.5 These effects and prevalence rates can be
found in Table 3.
DRUG INTERACTIONS
The immune response to Quadracel may be reduced when
it is taken concomitantly with immunosuppressive therapies,
including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids.5
Quadracel may be administered with the measles, mumps,
and rubella and varicella vaccines as long as they are administered with different syringes and at different injection sites.5,6
CONTRAINDICATIONS
Quadracel is contraindicated in children with hypersensitivity to any of the ingredients in the vaccine.5 In addition, it is
contraindicated in those with encephalopathy (e.g., prolonged
seizures, coma, decreased brain function) within seven days of
a prior dose of a vaccine containing pertussis and in children
with a progressive neurological disorder (e.g., progressive
encephalopathy, infantile spasms, uncontrolled epilepsy).5
WARNINGS AND PRECAUTIONS
Acute Allergic Reactions
Epinephrine hydrochloride solution and other appropriate
agents and equipment must be available for immediate use in
case of anaphylactic reaction or acute hypersensitivity.5
Adverse Reactions Following Prior Pertussis Vaccination
If any of the following events have occurred within a certain
time period after receiving a pertussis vaccination, the decision
to administer Quadracel should be based on careful consideration of benefits and risks:5
•Temperature of 105° F or higher within 48 hours, with
no other identifiable cause
•Collapse or shock-like state within 48 hours
•Persistent, inconsolable crying lasting three hours or
more within 48 hours
•Seizure with or without fever within three days
Guillain–Barré Syndrome
Guillain–Barré syndrome is an autoimmune disease in which
the body’s immune system attacks its own peripheral nerves
and damages the myelin insulation that surrounds the nerves.
Symptoms of weakness or a tingling sensation in the legs can
be seen with this syndrome.6,10 If these symptoms occur within
six weeks of administration of a vaccine containing tetanus
toxoid, the decision to give Quadracel should be based on
careful consideration of the potential benefits and possible
risks.5,10
Limitations of Vaccine Effectiveness
Quadracel may not protect all individuals and should not
be used in adults.5,11
Altered Immunocompetence
If administered to immunocompromised patients, including
those using immunosuppressive agents, the expected immune
response may not be obtained; therefore, immune protection
may not be provided against the intended diseases.5
DOSAGE AND ADMINISTRATION
Quadracel is a suspension for intramuscular injection only,
supplied in 0.5-mL single-dose vials.5,6 It is administered intramuscularly into the deltoid muscle of the upper arm. It should
not be administered directly into the veins.5,6,11 The vial must
be shaken just before use until a uniform, white, cloudy suspension results.5,6 Quadracel should not be reconstituted or mixed
with any other vaccine.5,6 If there are any signs of tearing or
tampering on the packaging, the vaccine should not be used.11
STORAGE AND HANDLING
Quadracel should be refrigerated and stored at 35º F to
46º F5 (2º C to 8º C).6 It should not be frozen. Any Quadracel
product that has been exposed or may have been exposed to
freezing should not be used because freezing destroys the
vaccine.5 Always check the expiration date on the label before
administering. Expired product should never be used.5,6
COST
The average wholesale price (AWP) for a 0.5-mL dose of
Quadracel is $119. In comparison, the combined AWP of the
separate DTaP and IPOL final vaccinations is $137. Pentacel,
a combination vaccine that may be considered instead of
Quadracel, is priced at $99 for a single dose.12
CONCLUSION
Quadracel should be recommended to parents who have
children between the ages of 4 and 6 years who meet the administration criteria and need to finalize their DTaP and IPV series.
Quadracel’s administration in the vaccination series replaces
one additional injection, which may benefit those children who
are afraid of receiving shots. This may also mean having one
less doctor’s appointment, which could benefit a parent or legal
guardian’s schedule. The cost of Quadracel is comparable to the
other vaccines that may be considered for this immunization,
so cost should not be an issue. Although the Quadracel vaccine
may not protect everyone who has received the vaccination, it
has proven to be both immunogenic and safe in clinical trials.
continued on page 253
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Vaccine Spotlight: Quadracel
continued from page 240
REFERENCES
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www.washingtonpost.com/news/to-your-health/wp/2014/06/26/
the-ethical-negligence-of-parents-who-refuse-to-vaccinate-theirchildren. Accessed August 19, 2015.
3. Centers for Disease Control and Prevention. Measles vaccination.
July 1, 2015. Available at: www.cdc.gov/measles/vaccination.html.
Accessed August 23, 2015.
4. Centers for Disease Control and Prevention. Measles cases and
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cases-outbreaks.html. Accessed February 25, 2016.
5. Quadracel (diphtheria and tetanus toxoids and acellular pertussis
adsorbed and inactivated poliovirus vaccine) prescribing information. Swiftwater, Pennsylvania: Sanofi Pasteur Inc. Available at:
www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/
ApprovedProducts/UCM439903.pdf. Accessed July 2, 2015.
6. Sturdy. Quadracel data sheet. November 1, 2007. Available at:
www.hisunim.org.il/images/documents/Package_Inserts/
Quadracel.pdf. Accessed July 2, 2015.
7. Centers for Disease Control and Prevention. 2015 recommended
immunizations for children from birth through 6 years old. Available at: www.cdc.gov/vaccines/parents/downloads/parent-versch-0-6yrs.pdf. Accessed July 2, 2015.
8. Sanofi Pasteur announces FDA approval of Quadracel DTaP-IPV
vaccine for children 4 through 6 years of age [press release].
Swiftwater, Pennsylvania: Sanofi Pasteur; March 24, 2015. Available
at: http://sanofipasteurus.mediaroom.com/2015-03-25-SanofiPasteur-Announces-FDA-Approval-of-Quadracel-DTaP-IPV-Vaccine-for-Children-4-through-6-Years-of-Age. Accessed July 2, 2015.
9. ClinicalTrials.gov. Study of DTap-IPV compared to DAPTACEL and IPOL as the 5th dose in children 4 to 6 years of age.
NCT01346293. May 28, 2015. Available at: https://clinicaltrials.
gov/ct2/show/study/NCT01346293. Accessed July 2, 2015.
10. Nordqvist C. What is Guillain-Barre syndrome? What causes
Guillain-Barre syndrome? Medical News Today. September 26,
2014. Available at: www.medicalnewstoday.com/articles/167892.
php. Accessed July 15, 2015.
11. Better Health Channel Website. Victoria Government. Quadracel. May 11, 2015. Available at: www.betterhealth.vic.gov.au/~/
media/bhc/files/medicine%20guides%20library/05/cmi5382.pdf.
Accessed: August 23, 2015.
12. Red Book Online. Ann Arbor, Michigan: Truven Health Analytics.
Accessed February 24, 2016. n
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