For Health Care Professionals only

PRN Hexavalent vaccine: Less Fever Less Pain

Helping healthcare professionals to protect infants against diseases

GlaxoSmithKline Indonesia
© 2022 GSK group of companies or its licensor

PM-ID-INH-PPT-220003 AD: 05/22 ED: 05/24

 Infanrix hexa has been extensively evaluated in both
clinical trials and real‑world practice

als
ic al tri
Clin
~100 >41,000 >21,000
studies infants toddlers
sponsored by GSK received primary received booster
during development1,2 vaccination, including doses3
>1,600 born preterm3,4

tice
pra c
orl d
Rea
l-w
>20 >90 >210 Help to
million protect
years countries >60
doses million
use in clinical have approved Infanrix distributed infants
practice5–7 hexa8 globally9*
(≈ 6 m
preterms)

*As of March 2022

1. EU Clinical Trials Register search. https://www.clinicaltrialsregister.eu/ctr-search/search?query=Infanrix+hexa+AND+GlaxoSmithKline+Biologicals (accessed July 2020);

2. ClinicalTrials.gov search. https://clinicaltrials.gov/ct2/results?term=+hexa&lead=GlaxoSmithKline (accessed July 2020); 3. GSK. Data on file, Number of Subjects 2016N287488_00;
4. Omeñaca F, et al. Vaccine 2018;36:986–96; 5. GSK. Infanrix hexa Product InformationI Version number: GDS20 IPI15 (16 January 2020) 2
.; 6. Zepp F, et al. Expert Rev Vaccines 2009;8:663–78;
7. Lyseng-Williamson KA, et al. Paediatr Drugs 2012;14:337–43; 8. GSK. Data on file, 2017N332737_01; 9. GSK. Data on file, 2022N504338_00
Infanrix hexa: >20 years of experience

1 2
What is Infanrix hexa? What is the safety profile of
Infanrix hexa?

3 4
Infanrix hexa in preterm
Clinical development and
infants
Real-world experience
What is Infanrix hexa?

Infanrix hexa is a combination vaccine targeting

six diseases* in infants and toddlers

Diphtheria
Tetanus
Pertussis
Hib†
Poliomyelitis
Hepatitis B

Primary dose Booster dose

Helps to protect Administered as either a Can be used in children

against six potentially 3+1 or 2+1 primary and >6 weeks of age§
serious diseases booster schedule‡

*Containing active substances derived from diphtheria, tetanus, pertussis and Hib bacteria, HBV, and inactivated polioviruses 1, 2 and 3
†
Hib is provided as a separate powder and must be reconstituted in the DTPa-HBV-IPV suspension before use
‡
Schedule dependent on locally-applied/recommended schedule as per local licensing
§
Safety and efficacy have not been established in children >36 months of age
DTPa, Diphtheria-tetanus-acellular pertussis; HBV; Hepatitis B virus; Hib, Hemophilus influenzae type b; IPV, Inactivated polio virus

GSK. Infanrix Hexa Prescribing Information, Version GDS18/IPI13.;

4
 DTaP Combination Vaccination:
Essential component of Child’s Immunization schedule

Diphtheria: Re-emergence & outbreaks 1

The disease was one of the most common causes of illness and death among children before a vaccine
was available2

Tetanus: endemic & an important health problem 3

The majority of reported tetanus cases are birth-associated among newborn babies and mothers who have
not been sufficiently vaccinated with a tetanus-toxoid-containing vaccines

Pertussis
Pertussis remains one of the leading causes of vaccine-preventable deaths worldwide, despite overall high
vaccination coverage. Most pertussis deaths occur in young babies who are either unvaccinated or
incompletely vaccinated. 4

Polio: risk of international spread of Poliovirus remains a Public Health Emergency of International
Concern5

Hib disease commonly affects children <5 years 6

was leading cause of bacterial meningitis in the prevaccine era 6

Hepatitis B: when infection is acquired in infancy and early childhood leads to chronic hepatitis in about
95% of cases.7
DTaP Diptheria Tetanus & Acellular Pertussis: HIV=Human immunodeficiency Virus, Hib= Haemophilus influenzae type b

1 Clarke K, MacNeil A, Hadler S, Scott C, Tiwari T, Cherian T. Global Epidemiology of Diphtheria, 2000–2010. Emerg Infect Dis. 2019;25(10):1834-1842. https://doi.org/10.3201/eid2510.190271 2. CDC Diphteria home; Surveillance. Last reviewed:
May 2020. https://www.cdc.gov/diphtheria/surveillance.html 3. WHO. Fact sheets. Tetanus/ May 2018. https://www.who.int/news-room/fact-sheets/detail/tetanus#:~:text=Key%20facts,%2Dcontaining%20vaccines%20(TTCV). (last accessed April
2022)/ 4. CDC. Fact https://www.cdc.gov/pertussis/countries/index. 5. https://www.who.int/news/item/11-03-2022-statement-of-the-thirty-first-polio-ihr-emergency-committee; 6 McNair, J et al. The Pediatric Infectious Disease Journal, 2018, 37(7):
726-728; 7. WHO. Hepatits B fact sheet. July 2021. available at: https://www.who.int/news-room/fact-sheets/detail/hepatitis-b 5
 Pertussis is a highly contagious respiratory disease that
causes paroxysms of intense coughing1,2

Respiratory infection • Coughing

caused by the Gram- • Characteristic ‘whoop’
negative bacterium
• Vomiting, sleep problems
Bordetella pertussis1
and exhaustion1–3
• Mild symptoms may also
occur in older children and
Cause Symptoms adults

Considerable underreporting of pertussis 6

• One case can lead to up to 17
cases in an unvaccinated
24.1 million cases population4
160,700 deaths • Asymptomatic carriers, => main
Global estimates (aged <5 years)7 sources of infection1,2
• Mothers = primary source of
53% of deaths in infants <1 year old infection of 0-3 months infants 5
Burden of Disease Contagiousness

1. World Health Organization (WHO). Wkly Epidemiol Rec 2015;35:433–460; 2. Centers for Disease Control and Prevention (CDC), 2018. Pertussis. In: The Pink Book: Epidemiology and
Prevention of Vaccine-Preventable Diseases. https://www.cdc.gov/vaccines/pubs/pinkbook/pert.html (accessed August 2018); 3. National Health Service (NHS) Choices, 2016. Whooping 6
cough. http://www.nhs.uk/Conditions/Whooping-cough/Pages/Introduction.aspx (accessed August 2018); 4. Kilgore PE et al. Clin Microbiol Rev 2016;29:449–486; 5. Bisgard KM et al.
Pediatr Infect Dis 2004;23:985–989; 6. . Wirsing von König CH et al. Pediatr Infect Dis J 2005;24:S87–92; 7. Yeung KHT et al. Lancet Infect Dis 2017;17:974–980
There are two types of pertussis vaccines available 1

Whole-cell vaccines (wP) Acellular vaccines (aP)

(containing antigenic components)

• Contain the whole bacterium, which has been • Contain several purified antigens: all aP vaccines contain PT
inactivated1 either alone or in combination with the adhesins FHA, PRN
and FIM1,3
• Highly reactogenic2
• Less reactogenic than whole-cell vaccines 2
• High inter-vaccine heterogeneity 2 • Better vaccine reproducibility than whole-cell vaccines 2

Since the 1980s, many countries have switched from whole-cell to acellular 7

pertussis vaccines, based on their improved safety profile1,4

aP, acellular pertussis; FHA, filamentous haemagglutinin; FIM, fimbriae; PRN, pertactin; PT, pertussis toxin; wP, whole-cell pertussis
1. World Health Organization. Wkly Epidemiol Rec 2015; 90:433–460. 2. Guiso N. Ther Adv Vaccines 2013; 1:59–66. 3. Edwards KM, Decker MD. Chapter 44: Pertussis vaccines. Plotkin’s Vaccines. 7th Edition. 2018. Elsevier,
Philadelphia. 4. Barkoff AM et al. Pathog Dis 2015; 73:ftv050.
Composition of Infanrix hexa

Antigen/adjuvant Infanrix hexa (0.5 mL)1

Diphtheria toxoid 30 IU
Tetanus toxoid 40 IU
Pertussis antigens
• Pertussis toxoid (PT) 25 µg
• FHA 25 µg
• Pertactin (PRN) 8 µg

Hepatitis B surface antigen 10 µg

Inactivated poliovirus
• Type 1 (Mahoney strain) 40 D
• Type 2 (MEF-1 strain) 8D
• Type 3 (Saukett strain) 32 D
10 µg
Hib polysaccharide (PRP) conjugated to
tetanus toxoid
0.32 mg AlPO4
Al3+ content
0.5 mg Al(OH)3

Al3+, aluminium ion; Al(OH)3, aluminium hydroxide; AlPO4, aluminium phosphate; D, Daltons; FHA, filamentous haemagglutinin; Hib, Haemophilus influenzae type b; IU, international
units; MEF, Middle East Forces; PRP, polyribosylribitol phosphate

1. GSK. Infanrix hexa EU SmPC. European Medicines Agency (EMA), 2022.

8
https://www.ema.europa.eu/documents/product-information/infanrix-hexa-epar-product-information_en.pdf;
Various roles of antibodies against antigens in aP
vaccines (PT, FHA, FIM)

PT, FHA and FIM*

FIM

Bp

A
Antibodies against PT and
FHA neutralise secreted
virulence factors and mitigate B
disease progression, but do
not target the bacterial Antibodies attaching the
surface
This figure is reproduced by GSK under CC-BY. These data were first published in Ma L et al. Emerg Infect Dis 2021; 27:294–297.
fimbriae poorly activate
the complement system
*FIM is not included in Infanrix Hexa
far from the bacterial
membrane
aP, acellular pertussis; Bp, Bordetella pertussis; FHA, filamentous hemagglutinin; FIM, fimbriae; PT, pertussis toxin

Ma L et al. Emerg Infect Dis 2021; 27:294–297.

9
Various roles of antibodies against antigens in aP
vaccines: Pertactin (PRN)

PRN*: the only aP vaccine antigen that remains closely associated with the outer membrane

C
Antibody-PRN complex
induces strong
bactericidal activity via
multiple synergistic
functions leading to cell
opsonization and
digestion by
phagocytes
Bp

PRN

Antibody

This figure is reproduced by GSK under CC-BY. These data were first published in Ma L et al. Emerg Infect Dis 2021; 27:294–297.

10
* PRN antigen is not included in Hexaxim

aP, acellular pertussis; Bp, Bordetella pertussis; CR1, complement receptor type 1; FcR, fragment crystalizable region; FIM, fimbriae; MAC, membrane attack complex; PRN, pertactin

Ma L et al. Emerg Infect Dis 2021; 27:294–297.

Various roles of antibodies against antigens in aP
vaccines: PRN

PRN: the only aP vaccine antigen that remains closely associated with the outer membrane

C
Antibody-PRN
complex induces
strong bactericidal
activity via multiple
synergistic
functions leading to
cell opsonization
and digestion by Bp
phagocytes
PRN

Antibody

This figure is reproduced by GSK under CC-BY. These data were first published in Ma L et al. Emerg Infect Dis 2021; 27:294–297.

11

aP, acellular pertussis; Bp, Bordetella pertussis; CR1, complement receptor type 1; FcR, fragment crystalizable region; FIM, fimbriae; MAC, membrane attack complex; PRN, pertactin

Ma L et al. Emerg Infect Dis 2021; 27:294–297.

Various roles of antibodies against antigens in aP
vaccines

PRN: the only aP vaccine antigen that remains closely associated with the outer membrane

Phagocyte
C
Antibody-PRN
complex induces
strong bactericidal
activity via multiple
synergistic functions
leading to cell
opsonization and
digestion by
phagocytes

This figure is reproduced by GSK under CC-BY. These data were first published in Ma L et al. Emerg Infect Dis 2021; 27:294–297.

12

aP, acellular pertussis; Bp, Bordetella pertussis; CR1, complement receptor type 1; FcR, fragment crystalizable region; FIM, fimbriae; MAC, membrane attack complex; PRN, pertactin

Ma L et al. Emerg Infect Dis 2021; 27:294–297.

Various roles of antibodies against antigens in aP
vaccines

PRN: the only aP vaccine antigen that remains closely associated with the outer membrane

Phagocyte
C
Antibody-PRN
complex induces
strong bactericidal
activity via multiple
synergistic
functions leading to
cell opsonization
and digestion by
phagocytes

This figure is reproduced by GSK under CC-BY. These data were first published in Ma L et al. Emerg Infect Dis 2021; 27:294–297.

13

aP, acellular pertussis; Bp, Bordetella pertussis; CR1, complement receptor type 1; FcR, fragment crystalizable region; FIM, fimbriae; MAC, membrane attack complex; PRN, pertactin

Ma L et al. Emerg Infect Dis 2021; 27:294–297.

Various roles of antibodies against antigens in aP
vaccines

PRN: the only aP vaccine antigen that remains closely associated with the outer membrane

Phagocyte
C
Antibody-PRN
complex induces
strong bactericidal
activity via multiple
synergistic
functions leading to
cell opsonization
and digestion by
phagocytes

This figure is reproduced by GSK under CC-BY. These data were first published in Ma L et al. Emerg Infect Dis 2021; 27:294–297.

14

aP, acellular pertussis; Bp, Bordetella pertussis; CR1, complement receptor type 1; FcR, fragment crystalizable region; FIM, fimbriae; MAC, membrane attack complex; PRN, pertactin

Ma L et al. Emerg Infect Dis 2021; 27:294–297.

Infanrix hexa: >20 years of experience

1 2
What is Infanrix hexa? What is the safety profile of
Infanrix hexa?

3 4
Infanrix hexa in pre-terms
Clinical development and
Real-world experience
More than 17 years of post-marketing safety surveillance 1
Safety profile of Infanrix hexa administered as a 2+1 or 3+1 schedule

159 million doses delivered globally until

Database lock in October 2017
Frequency per 100,000 doses
No reported interruptions to vaccination Fever 7.74
programs due to safety issues* Crying 2.62
Injection site 1.87
The 10 most frequently spontaneously erythema
reported events occurred at a frequency Swelling 1.28
of ≤7.8 per 100,000 doses†1 Injection site 0.92
pain
Irritability ≤0.90
Reporting of preparation errors (mostly Vomiting
reconstitution) was low and did not impact Somnolence
the vaccine’s benefit-risk profile1 Hypotonia

*Information correct to the knowledge of GSK

†
Analysis based on 31,892 spontaneous AE reports following vaccination with DTPa-HBV-IPV/Hib after distribution of 159,713,190 doses worldwide up to 22 October 2017 (database
lock). Inappropriate schedule of vaccine administration not included in table had a reporting rate of 0.95 per 100,000 doses

1. Gomèz P, et al Exp Rev Vaccine 2020. https://www.tandfonline.com/doi/pdf/10.1080/14760584.2020.1800458

16
 Meta-analysis of head-to-head safety endpoints for
Infanrix hexa compared to Hexaxim1

Systematic review and

meta-analysis of 9 direct, 6 studies* of primary Pooled ORs statistically significantly
vaccination included in the lower with Infanrix hexa than Hexaxim
head-to-head phase for 9/12 safety endpoints
IIIRCTs analysis (N=4,314)

Systemic reactions: OR (95%CI)

Local reactions: OR (95% CI)
Fever 0.67 (0.54–0.83)
Pain 0.74 (0.62–0.89)
Drowsiness 0.82 (0.71–0.94)

Irritability 0.82 (0.69–0.95)

Redness 0.72 (0.63–0.83)
Persistent crying 0.72 (0.61–0.84)

Anorexia 0.83 (0.72–0.95)

Swelling 0.86 (0.74–0.99) Vomiting

0.96 (0.83–1.11)
Any Grade 3 0.71 (0.58–0.88)

Any Grade 3 0.81 (0.64–1.02)

Any discontinuation
0.99 (0.60–1.61)

Favours Favours 0 1
0 1 Favours Favours
Infanrix hexa Hexaxim Infanrix hexa Hexaxim

Orange markers indicate outcomes for which there was a statistically significant difference between Infanrix hexa and Hexyon.

*Three studies were excluded as the publications only reported information on boosters. The same results were first published in Mukherjee, 2019. AE, adverse event; CI, confidence
interval; OR, odds ratio; RCT, randomised controlled trial

1. Mukherjee P et al. Expert Rev Vaccines. 2021 Mar;20(3):319-330

Real-life practice: fewer children would experience Adverse
Reactions with Infanrix hexa compared with Hexaxim

For every 100 children vaccinated, use of Infanrix Hexa over Hexaxim
would avert, on average:

10 cases of fever 7 cases of redness 6 cases of pain 4 cases of Grade 3

systemic reactions

AR not experienced with either vaccine AR experienced with both vaccines AR averted with DT3aP-HBV-IPV/Hib vs DT2aP-HBV-IPV-Hib

AR, adverse reaction. Figure adapted from Mukherjee P et al. 2021 with permission from Taylor & Francis

Mukherjee P et al. Expert Rev Vaccines 2021; DOI: 10.1080/14760584.2021.1892493 18

Infanrix hexa has a similar tolerability profile in preterm
and full term infants1
2 4 6

Cardiorespiratory events2

i
3 episodes of apnoea reported in 2 preterm infants; all resolved with stimulation
11/31 infants hospitalised at first immunisation experienced a resurgence/increase in
bradycardia/desaturation episodes; 2/31 experienced isolated desaturation episodes*

100 Full term (N=276 diary cards† [N=92 infants])

Preterm (≥24 weeks; N=281 diary cards † [N=94 infants])
80

Local General
Incidence (%)

60
symptoms2 symptoms2
40
28
18 18 17 17 19
20 16 14 14 15
13 13 12
6
0
Pain Redness Swelling Fever Irritability Appetite Drowsiness
loss

*
Episodes occurred within 72 hours after vaccination, all 13 infants were <28 weeks of gestational age
†
Diary cards were used by parents or research staff to record local and general symptoms

1. GSK. Infanrix hexa EU SmPC. European Medicines Agency (EMA), 2022.

19
https://www.ema.europa.eu/documents/product-information/infanrix-hexa-epar-product-information_en.pdf (accessed November 2019); 2. Omeñaca F. et al.
Pediatrics 2005;116:1292–1298
Infanrix hexa is generally well tolerated when
administered together with other vaccines 1

Meningococcal >30 studies including 21,000 subjects have demonstrated

Bexsero  that Infanrix hexa, when co-administered with 12 different
Meningitec
NeisVac-C


vaccines in infants including pneumococcal, and rotavirus
Nimenrix
Menjugate


vaccines, produces immunogenicity with a tolerable safety
profile1,2
Pneumococcal

Synflorix 
Prevnar 
Prevnar 13 
Observations when co-administering
Rotavirus Infanrix hexa with other vaccines:
Rotarix  Pneumococcal vaccines1,2
RotaTeq 
Increased rate of fever*; mostly moderate (≤39°C)
MMR, MMRV
and transient
Priorix-Tetra 
ProQuad  Potential increased risk of convulsions and
HHE after co-administration with PCV13 2

Prophylactic administration of antipyretics before or immediately after vaccine administration can reduce the incidence and intensity of post-vaccination febrile reactions. The use of
prophylactic antipyretic medicinal products is recommended for children with seizure disorders or with a prior history of febrile seizures 2
Please see slide notes for additional information
*Versus Infanrix hexa alone
HHE, Hypotonic hyporesponsive episode; MMRV, Measles, mumps, rubella and varicella
1. Dolhain J, et al. Expert Rev Vaccines. 2020;19(5):419–43; 2. GSK. Infanrix Hexa Prescribing Information, Version GDS18/IPI13.
20
Infanrix hexa: >20 years of experience

1 2
What is Infanrix hexa? What is the safety profile of
Infanrix hexa?

3 4
Clinical development and
Infanrix hexa in preterms infants
Real-world experience
The World Health Organization (WHO) defines preterm birth
as any birth before 37 weeks of gestation*1,2

Most preterm births happen between 32 and 37 weeks of gestation

5.2% 10.4% 84.3%

Weeks 28 32 37 40

Extremely Very preterm Moderate-to-late

preterm preterm

Most newborns with very-low birthweight (VLBW; <1500 g) are preterm

However, although birthweight is closely linked with gestational age,
the terms cannot be used interchangeably as there is a range of ‘normal’
birthweights
for a given gestational age, gender and ethnicity 1

*Births at 37 to 39 weeks still have suboptimal outcomes, and induction or caesarean birth should not be planned before 39 completed weeks unless medically indicated

1. World Health Organization (WHO), 2012. Born too soon. Global action report on preterm birth.
http://www.who.int/pmnch/knowledge/publications/preterm_birth_report /en/index1.html; 2. World Health Organization (WHO), 2018. Preterm birth. Fact sheet No. 363. 22
http://www.who.int/mediacentre/factsheets/fs363/en/. URLs accessed March 2022
More than 10% of infants are born preterm and the rate is
increasing worldwide1,2

Rates of preterm birth are 5–18% across 184 countries, 20101,3

1 in 10 babies (15 million) are

born preterm every year1,2

Incidence of preterm birth

increased by 10% from 2 million <10%
10–<15%

in 1990 to 2.2 million in 20101* ≥15%

Data not available

Figure reprinted from The Lancet, Vol. 379, Blencowe H et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for
selected countries: a systematic analysis and implications, pp. 9–15, Copyright 2012, with permission from Elsevier
*Data from 65 countries in Europe, the Americas, and Australasia, which includes almost all countries with national reported time series

1. World Health Organization (WHO), 2012. Born too soon. Global action report on preterm birth. 23
http://www.who.int/pmnch/knowledge/publications/preterm_birth_report/en/index1.html; 2. World Health Organization (WHO), 2018. Preterm birth. Fact sheet No. 363.
http://www.who.int/mediacentre/factsheets/fs363/en/; 3. Blencowe H et al. Lancet 2012;379:2162–2172. URLs accessed March 2022
 Preterm birth is associated with increased risk of morbidity
and mortality1,2

Preterm birth complications are among the leading causes of

death
globally in children aged <5 years1

Preterm infants may experience impaired immune

functioning, placing
them at higher risk of infectious disease. Reasons include: 2

Immature physical Impaired innate and Reduced time for

barriers against adaptive immune placental transfer of
infection (skin, mucosa) responses maternal antibodies

24
1. Liu L et al. Lancet 2015;385:430–440; 2. Baxter D. Hum Vaccin 2010;6:494–505
 Preterm and LBW infants are at increased risk of
infections and hospitalisations from vaccine preventable
diseases1

Pertussis

hospitalisation in preterm vs full-term infants Invasive pneumococcal disease

2x (IRR: 1.99, 95% CI: 1.47–2.71)2
infection in LBW‡ infants
2.6x
(RR: 2.6; P=0.03 vs infants ≥2500 g)4
severe disease with a history of
5x prematurity
(OR: 5.00; 95% CI: 1.27–19.71)3 infection in very preterm (<32 weeks) infants
9x (RR: 9.1 vs full-term infants)4

Rotavirus gastroenteritis Influenza

hospitalisation in VLBW* and LBW† infants severe disease in children with history of prematurity
2.6x (OR: 2.6; 95% CI: 1.6–4.1 and OR: 1.6; 95% CI: 1.3–2.1, vs full- 2.5x (OR: 2.53; 95% CI: 1.34–4.77)6
term infants respectively)5

*<1500 g; †1500–2499 g; ‡≤2500 g

CI, confidence interval; IRR, incidence rate ratio; LBW, low birthweight; OR, odds ratio; RR, risk reduction; VLBW, very-low birthweight

25
1. Gagneur A et al. Hum Vaccin Immunother 2015;11:2556–2563; 2. Riise ØR et al. Pediatr Infect Dis 2017;36:e151–e156; 3. Marshall H et al. Pediatr Infect Dis 2015;34:339–345;
4. Shinefield H et al. Pediatr Infect Dis J 2002;21:182–186; 5. Newman R et al. Pediatrics 1999;103:E3; 6. Garcia M et al. Epidemiol Infect 2015;143:2939–2949
 In practice, vaccination is frequently delayed in preterm
infants1,2
Several factors may explain why vaccination is often
delayed in preterm infants:2–4
26%
o Limited knowledge about vaccine effectiveness
Low-birthweight infants are more likely to
have delayed vaccination compared o Safety concerns and fear of adverse events
with normal- birthweight infants (OR,
1.26)1* o Insufficient information given to parents and care
Very-low-birthweight infants receive providers
routine vaccines significantly later
o Fear of prolonged hospitalisation of infant
than
normal-birthweight infants1*
o Preterm birth is commonly misperceived as a
contraindication for vaccination

In most cases, it is recommended that preterm and low-birthweight infants be vaccinated

• at the same chronological age1–7

• using the same schedule3–5 as full-term or normal-birthweight infants,
according to standard guidelines

*Low birthweight defined as <2500g, very-low birthweight as <1000g and normal birthweight as ≥2500g

26
1. Bart-Weisberg D, Stein-Zamir C. Hum Vaccin Immunother 2021;17:1666–1674; 2. Gagneur A et al. Hum Vaccin Immunother 2015;11:2556–2563; 3. McCrossan P et al. Public
Health 2015;129:896–898; 4. Kroger AT et al. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices
(ACIP). www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf (accessed March 2022)
Infanrix hexa extensively studied in pre-terms

Infanrix hexa has data from 10 studies involving >1600 individuals (Omeñaca 2018)

Countries Population Study arms

Australia 38 preterm (23–32 weeks) with • Infanrix hexa + PCV7 + RRV
post-immunisation apnoea • Infanrix-IPV + HBV-Hib + PCV7 + RRV

Switzerland 64 preterm VLBW (mean • Infanrix hexa

Infanrix
26.6 weeks; hexa
all <32 weeks) studies included >1600 infants: • Infanrix-IPV/Hib ± PCV7 or RSV
- LBW and VLBW infants (down to 500g)
Italy 79 preterm (≥32 weeks); • Infanrix hexa + MenC
74 full-term- Very preterm infants (GA down to 24 weeks)
- infants that experienced post immunization apnoea
Poland, Spain 99 preterm (<29 weeks– • Infanrix hexa + PCV13 + MenC
<37 weeks); - 98Infants
full-termwith history of bradycardia and apnoea
Switzerland 53 infants with history of apnoea/bradycardia (≥25 weeks) • Infanrix hexa
• Infanrix-IPV/Hib

Belgium 22 pretermInfanrix hexa

(25–30 weeks) studies on immunogenicity: • Infanrix hexa
- Covered all antigens
Spain, Greece 137 preterm (≥27 weeks); • Infanrix hexa + PHiD-CV
- Have follow up to 4 YOA
149 full-term • Infanrix-IPV/Hib + PHiD-CV

Spain 94 preterm (≥24 weeks); • Infanrix hexa

92 full-term
Argentina 82 LBW; 79 VLBW (all ≥24 weeks) • Infanrix hexa

France, Portugal, Poland, 1008 preterm (≥27 weeks) • Infanrix hexa + HRV
Spain • Infanrix + IPV + Hib
• Infanrix-IPV/Hib (±HBV and/or PCV7)
Data from 10 clinical trials support the use of Infanrix
Hexa in preterm and LBW or VLBW infants1

Extensively 10 clinical trials have evaluated use in preterm infants (≥24 weeks 3), with >1600 preterm
evaluated1–3 infants included

Immunogenic2‒4 Similar levels of seropositivity/ seroprotection in preterm infants and full-term infants*

Well tolerated1,3‒5 Clinically acceptable safety profile in preterm, LBW and VLBW infants †
Potential risk of apnoea for very preterm infants (≤28 weeks)‡

Additional Combination vaccines can facilitate timely immunisation of infants who are at increased risk
benefits1,3 of infectious disease. DT3aP-HBV-IPV/Hib is well tolerated in co-administration regimens in preterm infants§

*However, a lower immune response may be observed for some antigens; †Includes preterm infants born with low birthweight (1.5 kg–2.0 kg) and VLBW (<1.5 kg); ‡Potential risk of
apnoea and the need for respiratory monitoring for 48‒72 h should be considered for very preterm infants (born ≤28 weeks of gestation); §Co-administration with pneumococcal conjugate
vaccines, rotavirus vaccines and meningococcal vaccines. 3 LBW, low birthweight; VLBW, very-low birthweight

28
1. Omeñaca F et al. Vaccine 2018;36:986–96; 2. Omeñaca F et al. Pediatrics 2007;119:e179; 3. GSK. Infanrix hexa EU SmPC. EMA, 2022.
https://www.ema.europa.eu/documents/product-information/infanrix-hexa-epar-product-information_en.pdf (accessed March 2022); 4. Omeñaca F et al. Pediatrics 2011;128:e290–
8; 5. Vázquez L et al. Acta Paediatr 2008;26:824–9
Infanrix hexa: >20 years of experience

1 2
What is Infanrix hexa? What is the safety profile of
Infanrix hexa?

3 4
Clinical development and
Infanrix hexa in preterms infants
Real-world experience
High seroprotection/seropositivity rates for all antigens
after primary and booster vaccinations with a 3+1 schedule
Primary schedule: first 12 months of life Booster
Months Months Months EPI schedule† 2nd year of life
(weeks)
2 4 2 6 3 5 6 14

3 4 4 10
Seroprotection/
seropositivity*

≥96.4% ≥96.6% ≥96.8% ≥95.7% ≥98.4%

N=196 N=1,693 N=1,055 N=265 N=2,009

2 studies 6 studies 6 studies 1 study 12 studies

*Seroprotective thresholds: anti-diphtheria, ≥0.1 IU/mL; anti-tetanus, ≥0.1 IU/mL; anti-HBs, ≥10 mIU/mL; anti-polio, ≥1/8 dilution; anti-PRP, ≥0.15 g/mL; seropositivity thresholds:
pertussis antigens PT, FHA, PRN ≥5 EL.U/mL
†
EPI schedule (at 6, 10, 14 weeks of age) may only be used if a dose of hepatitis B vaccine has been given at birth
EL.U, Enzyme-linked immunosorbent assay test unit; EPI, Expanded program of immunization; FHA, Filamentous hemagglutinin; HB, Hepatitis B surface antigen; IU, International unit;
PRN, Pertactin; PRP, Polyribosylribitol phosphate; PT, Pertussis toxoid

GSK. Infanrix Hexa Prescribing Information, Version GDS18/IPI13.

30
Up to 7 years of immune persistence across vaccine
antigens* with a 3+1 schedule1–3
4–6 years old (N=203)1 7–9 years old (N=200)1
3, 4, 5 or 2, 3, 4 months + 12–23 months 3, 4, 5 months + 12–24 months

Diphtheria Tetanus Pertussis HBV Hib Polio

100
Patients with seroprotection/
seropositivity, % (95% CI)

80

60

40

20

0
Anti-diphtheria Anti-tetanus* Anti-PT* Anti-FHA Anti-PRN Anti-HBs Anti-PRP Anti-polio type1 Anti-polio type2 Anti-polio type3

4‒6 years old (N=174–198) 7‒9 years old† (N=51–193)

*Waning of PT and tetanus antibodies is countered by pre-school booster dose

†
These data are for children who had not received an additional booster of the antigens for DTPa-HBV-IPV/Hib following the booster in the 2 nd year of life (3+1 schedule);
DTPa, Diphtheria-tetanus-acellular pertussis; ELISA, Enzyme-linked immunosorbent assays; FHA, Filamentous hemagglutinin; HB, Hepatitis B surface antigen; HBV, Hepatitis B virus;
Hib, Hemophilus influenzae type b; IPV, Inactivated polio virus; PRN, Pertactin; PRP, Polyribosylribitol phosphate; PT, Pertussis toxoid

Figure created from data tables in Data on file, 2014N203547_01

31
1. Zinke M, et al. Hum Vaccin 2010;6:189–93; 2. GSK. Data on file, 2014N203547_01 – Infanrix hexa persistence data presented in Zinke, et al. 2010;
3. GSK. Data on file, 2014N203547_00 – Infanrix hexa persistence data presented in Zinke, et al. 2010
Up to 15 years of immune persistence to HBV with a
3+1 schedule

Vaccination schedule (months) At 14–15 years of age,

administration of challenge
2 3 4 12–15 dose to mimic HBV
exposure (N=268)2

98.4% 92.5%
(N=2,009) (95% CI 88.7–95.4)
had seroprotective antibody produced an
titers against HBV anamnestic response† to
1 month after booster dose*1 HBV exposure challenge

*Pooled across different primary vaccination schedules

†
Anamnestic response was defined as anti-HBs concentrations ≥10 mIU/mL in participants seronegative (anti-HBs antibody concentrations <6.2 mIU/mL) before the challenge dose
and as a ≥4-fold increase in anti-HBs concentrations in participants seropositive (anti-HBs antibody concentrations ≥6.2 mIU/mL) before the challenge dose
HB, Hepatitis B surface antigen; HBV, Hepatitis B virus; CI, confidence interval

1. GSK. Infanrix Hexa Prescribing Information, Version GDS18/IPI13; 2. Schwarz TF, et al. Hum Vaccin Immunother 2019;15:235–41
32
A 3-dose primary vaccination schedule provides high
vaccine efficacy against pertussis
German household
Italian randomized, double-blind study2,3
contact study1
Primary schedule (months) Primary schedule (months) 5-year unblinded follow-up
3 5 2 6 at 3–6 years of age3

4 4

88.7% 83.9% 86.0%

vaccine efficacy* vaccine efficacy* vaccine efficacy†

N=22,505 N=4,481 N=4,217

Cases=360 Cases=37 Cases=33

*As of 1 month after dose 3; †At up to 60 months since last priming dose; N, number of patients vaccinated
Please note: these results have been obtained with DTaP Infanrix containing same antigen, in the same amount as Infanrix Hexa: 1,3,4 Equivalence in efficacy is based on the comparison of antibody titres
between Infanrix and Infanrix hexa
DTaP, Diphtheria-tetanus-pertussis

1. Schmitt HJ, et al. JAMA 1996;275:37–41; 2. Greco D, et al. N Engl J Med 1996;334:341–8; 3. Salmaso S, et al. Pediatrics 2001;108:E81; 4. GSK. Infanrix Hexa Prescribing
33
Information, Version GDS18/IPI13.
Pertussis components* of Infanrix hexa prevents
hospitalization due to pertussis

Vaccine effectiveness increased significantly with each consecutive dose

2 4 6 15–24

98% 100%
100 84%
90
pitalization, % (95%
ness against hos-
Vaccine effective-

80
70 42%
VE against hospitalization was
60 100% (95% CI 97.9–100) in
50 infants who completed a 3+1
CI)

40
30 primary course
20
10
0
Dose 1 Dose 2 Dose 3 Dose 4

Dose 1 Dose 2 Dose 3 Dose 4

Children observed 19,670 19,580 19,442 17,856

Number of cases 36 11 6 0

*Note the publication mentions the vaccine as being the 3aP GSK vaccine, during the study period DTaP-IPV (Infanrix-IPV), DTaP-IPV/Hib (Infanrix IPV-Hib) and DTaP-IPV-HB/Hib
(Infanrix Hexa) were available (GSK market knowledge), but the proportion of vaccines used in this study are unspecified. CI, confidence interval; DTaP, Diphtheria-tetanus-pertussis
VE, vaccine effectiveness
Graph independently created by GSK based on data from Table 1 in Mack I, et al. Vaccine 2020;38:1444–9
Hexavalent vaccines are effective against invasive Hib
disease with a 3-dose schedule
In a German post-marketing study:

Follow-up Vaccine Number of doses Vaccine effectiveness, % (95% CI)

90.4 (70.6–96.8)
5 years 1
Two hexavalent vaccines
(N=2,893) (including Infanrix hexa)
100 (52.7–100)

89.6 (74.4–95.8)
7 years2,3 Two hexavalent vaccines
(N=2,851) (including Infanrix hexa)
100 (99.9–100)

CI, confidence intervals; Hib, Hemophilus influenzae type b

1. Kalies H, et al. Vaccine 2008;26:2545–52; 2. Infanrix Hexa Prescribing Information, Version GDS18/IPI13.; 3. GSK. Data on file 2020N436414_00
35
Sustained Hib control with Infanrix Hexa
Disease reduction in European children

Sustained decline in Hib infections among children aged <1 and 1–4 years
of age with increased vaccine coverage
2.5

Hib vaccine coverage in <1-year-olds (%)

100
Hib notification rate (per 100,000)

Infanrix hexa since 2006

2
80

1.5
60

1 40

0.5 20

0 0
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Hib rate in people aged (years): Vaccine coverage in <1-year-olds:

<1 1–4 65+
Graph constructed using data from the EU Invasive Bacterial Infections Surveillance Network and the European Surveillance System database from 1999 to 2014. There were
17–20 participating countries within the EU/European Economic Area in early years. From 2008, the number of participating countries increased to 29 (including the UK)
Hib, Hemophilus influenzae type b

Figure reproduced from Wang S, et al. A review of Hemophilus influenzae disease in Europe From 2000–2014: challenges, successes and the contribution of hexavalent
36
combination vaccines. Expert Rev Vaccines 2017;16:1095–105, reprinted by permission of the publisher Taylor & Francis Ltd, http://www.tandfonline.com
Summary: Infanrix hexa

The only 6-in-1* vaccine with

>20 years of clinical use2,6

Widest documented Highly immunogenic and well

co-administration options tolerated across a range of
of any hexavalent vaccine1–3 standard vaccination schedules4

The only 6-in-1 vaccine supported

Up to 7 years immune persistence
by safety and immunogenicity data
measured against all
from prospective trials in
vaccine antigens1†
preterm infants1,2,5

Extensive post‑marketing surveillance

shows acceptable tolerability in full-term
and preterm infants1,5

*Containing active substances derived from diphtheria, tetanus, pertussis and Hemophilus influenzae type b bacteria, the hepatitis B virus, and inactivated polioviruses 1, 2 and 3
†
Up to 15 years immune persistence against hepatitis B has been demonstrated

1. GSK. Infanrix Hexa Prescribing Information, Version GDS18/IPI13.; 2. Sanofi Pasteur SA. Hexaxim EU SmPC. EMA, 2021; 3. Dolhain J, et al. Expert Rev Vaccines.
37
2020;19(5):419–43.; 4. Zepp F, et al. Expert Rev Vaccines 2009;8:663–78; 5. Omeñaca F, et al. Vaccine 2018;36:986–96.; 6. GSK. Infanrix hexa EU SMPC. EMA, 2019.;
Infanrix hexa succinct safety information

Contraindications: Hypersensitivity: to the active substances or to any of the excipients or residues, after previous administration of diphtheria,
tetanus, pertussis, hep B, polio or Hib vaccines. Contraindicated if the child has experienced an encephalopathy of unknown aetiology, occurring
within 7 days following previous vaccination with pertussis containing vaccine. In these circumstances pertussis vaccination should be discontinued
and the vaccination course should be continued with diphtheria-tetanus, hep B, inactivated polio and Hib vaccines.

Warnings and Precautions: If any of the following events are known to have occurred in temporal relation to receipt of pertussis-containing vaccine,
the decision to give further doses should be carefully considered: Temperature of ≥40.0°C within 48 hours, not due to another identifiable cause;
Collapse or shock-like state (hypotonic - hyporesponsive episode) within 48 hours of vaccination; persistent, inconsolable crying lasting ≥ 3 hours
within 48 hours of vaccination; Convulsions with or without fever, occurring within 3 days of vaccination. Infanrix hexa contains traces of neomycin
and polymyxin. A protective immune response may not be elicited in all vaccinees. Data from clinical studies indicate that, when Infanrix Hexa is co-
administered with pneumococcal conjugate vaccine, the rate of febrile reactions is higher compared to that occurring following the administration of
Infanrix Hexa alone. Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed
with concomitant administration of Infanrix hexa and Prevenar.

Special Population: The potential risk of apnoea and the need for respiratory monitoring for 48-72h should be considered when administering the
primary immunization series to very preterm infants (born ≤28 weeks of gestation) and particularly for those with a previous history of respiratory
immaturity. As the benefit of vaccination is high in these infants, vaccination should not be withheld or delayed. Safety profile Infanrix hexa in infants
and toddlers born to mothers vaccinated with dTpa during pregnancy was similar regardless of exposure/non-exposure to dTpa during pregnancy.
Interaction: can be given concomitantly with pneumococcal conjugate, MenC conjugate, MenACWY conjugate, rotavirus, measles, mumps, rubella
and varicella vaccines. When Infanrix hexa is co-administered with PCV, the rate of febrile reactions is higher compared to that occurring following
the administration of Infanrix hexa alone.

Adverse Reactions: Very Common (≥1/10): appetite lost, irritability, crying abnormal, restlessness, pain, redness, local swelling at the injection site
(≤50 mm), fever ≥ 38°C, somnolence. Common (≥1/100 to <1/10): nervousness, vomiting, diarrhea, pruritus, local swelling at the injection site (>50
mm), fever >39.5°C, injection site reactions, including induration.

Infanrix hexa. BPOM Approved PI Version number: GDS20 IPI15 (16 January 2020)
Abbreviated Product Information of Infanrix hexa

Name of medicinal product: Infanrix Hexa (Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA)
(HBV), poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b vaccine (adsorbed)); Qualitative & quantitative
composition: Diphtheria toxoid not less than 30 International units (IU); Tetanus toxoid not less than 40 IU; Bordetella pertussis antigen :
Pertussis toxoid 25 µg; Filamentous Haemagglutinin 25 µg; Pertactin 8 µg; Hep B surface antigen 10 µg; Poliovirus (inactivated): type 1
(Mahoney strain) 40 D-antigen unit; type 2 (MEF-1 strain) 8 D-antigen unit; type 3 (Saukett strain) 32 D-antigen unit; Haemophilus
influenzae type b polysaccharide 10 µg - conjugated to tetanus toxoid as carrier protein 25 µg; Indications: Infanrix Hexa is indicated for
primary vaccination of infants and booster vaccination of toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and
Haemophilus influenzae type b; The use of Infanrix hexa should be in accordance with official recommendations. Dosage and
Administration: Primary vaccination consists of two or three doses (of 0.5 mL) which should be administered according to official
recommendations. Infanrix hexa can be considered for the booster if the antigen composition is in accordance with the official
recommendations. Full term infants and Preterm infants born after at least 24 weeks of gestational age: Primary vaccination: 3-
dose (There should be an interval of at least 1 month); Booster vaccination should be at least 6 months after the last priming dose and
preferably before 18 months of age. Full term infants: Primary vaccination: 2-dose (There should be an interval of at least 1 month);
Booster vaccination should be at least 6 months after the last priming dose and preferably between 11 and 13 months of age.The
Expanded Program on Immunization schedule (at 6, 10, 14 weeks of age) may only be used if a dose of hep B vaccine has been given at
birth. Where a dose of hep B vaccine is given at birth, Infanrix Hexa can be used as a replacement for supplementary doses of hep B
vaccine from the age of 6 weeks. Infanrix hexa is for deep intramuscular injection. Contraindications: Hypersensitivity: to the active
substances or to any of the excipients or residues, after previous administration of diphtheria, tetanus, pertussis, hep B, polio or Hib
vaccines. Contraindicated if the child has experienced an encephalopathy of unknown aetiology, occurring within 7 days following
previous vaccination with pertussis containing vaccine. In these circumstances pertussis vaccination should be discontinued and the
vaccination course should be continued with diphtheria-tetanus, hep B, inactivated polio and Hib vaccines. Warnings and Precautions:
If any of the following events are known to have occurred in temporal relation to receipt of pertussis-containing vaccine, the decision to
give further doses should be carefully considered: Temperature of 40.0°C within 48 hours, not due to another identifiable cause;
Collapse or shock-like state (hypotonic - hyporesponsive episode) within 48 hours of vaccination; persistent, inconsolable crying lasting
3 hours within 48 hours of vaccination; Convulsions with or without fever, occurring within 3 days of vaccination. Infanrix hexa contains
traces of neomycin and polymyxin. A protective immune response may not be elicited in all vaccinees. Data from clinical studies indicate
that, when Infanrix Hexa is co-administered with pneumococcal conjugate vaccine, the rate of febrile reactions is higher compared to
that occurring following the administration of Infanrix Hexa alone. Increased reporting rates of convulsions (with or without fever) and
hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of Infanrix hexa and Prevenar.

39
Prescribing information

Special Population: The potential risk of apnoea and the need for respiratory monitoring for 48-72h should be considered
when administering the primary immunization series to very preterm infants (born ≤28 weeks of gestation) and particularly
for those with a previous history of respiratory immaturity. As the benefit of vaccination is high in these infants, vaccination
should not be withheld or delayed. Safety profile Infanrix hexa in infants and toddlers born to mothers vaccinated with
dTpa during pregnancy was similar regardless of exposure/non-exposure to dTpa during pregnancy. Interaction: can be
given concomitantly with pneumococcal conjugate, MenC conjugate, MenACWY conjugate, rotavirus, measles, mumps,
rubella and varicella vaccines. When Infanrix hexa is co-administered with PCV, the rate of febrile reactions is higher
compared to that occurring following the administration of Infanrix hexa alone. Adverse Reactions: Very Common
(≥1/10): appetite lost, irritability, crying abnormal, restlessness, pain, redness, local swelling at the injection site (≤50 mm),
fever 38°C, somnolence. Common (≥1/100 to <1/10): nervousness, vomiting, diarrhea, pruritus, local swelling at the
injection site (>50 mm), fever >39.5°C, injection site reactions, including induration.

Abbreviated PI based on BPOM Approved PI Version number: GDS 20/IPI 15/ Date of issue: 16 January 2020
Before prescribing, please consult to PI (Product Information) which is available on request
Adverse events should be reported to GlaxoSmithKline Indonesia via email to yqq68540@gsk.com
Version 01 – May 2021

40
 For Health Care Professionals only

Before prescribing, please refer to the PI (Prescribing Information) which is available upon
request
Adverse Events should be reported to GlaxoSmithKline Indonesia via email
yqq68540@gsk.com

PM-ID-INH-PPT-220003 AD: 05/22 ED: 05/24

© 2020 GSK group of companies or its licensor

Trade marks are owned by or licensed to the GSK group of companies.

GlaxoSmithKline Indonesia
Menara Standard Chartered 35th floor, Jl. Prof. DR. Satrio No.164, Jakarta 12930
Tel (62-21)2553 2350 Fax (62-21)2553 2360

41