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HIGHLIGHTS OF PRESCRIBING INFORMATION • Vial and prefilled syringe presentation: a single dose after reconstitution
These highlights do not include all the information needed to use is approximately 0.5 mL. (3)
HIBERIX safely and effectively. See full prescribing information for
HIBERIX. ------------------------------ CONTRAINDICATIONS ------------------------------
Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any
HIBERIX [Haemophilus b Conjugate Vaccine (Tetanus Toxoid H. influenzae type b- or tetanus toxoid-containing vaccine or any component
Conjugate)] for injection, for intramuscular use of HIBERIX. (4)
Initial U.S. Approval: 2009
----------------------- WARNINGS AND PRECAUTIONS -----------------------
--------------------------- RECENT MAJOR CHANGES --------------------------- • If Guillain-Barré syndrome has occurred within 6 weeks of receipt of a
Dosage and Administration (2) 12/2023 prior vaccine containing tetanus toxoid, the decision to give HIBERIX
should be based on potential benefits and risks. (5.1)
• Syncope (fainting) can occur in association with administration of
--------------------------- INDICATIONS AND USAGE----------------------------
injectable vaccines, including HIBERIX. Procedures should be in place to
HIBERIX is a vaccine indicated for active immunization for the prevention of
avoid falling injury and to restore cerebral perfusion following syncope.
invasive disease caused by Haemophilus influenzae type b. HIBERIX is
(5.2)
approved for use in children aged 6 weeks through 4 years (prior to fifth
birthday). (1) • Apnea following intramuscular vaccination has been observed in some
infants born prematurely. Decisions about when to administer an
----------------------- DOSAGE AND ADMINISTRATION ----------------------- intramuscular vaccine, including HIBERIX, to infants born prematurely
For intramuscular administration only. should be based on consideration of the individual infant’s medical status,
A 4-dose series (either 0.5 mL or approximately 0.5 mL each, depending on and the potential benefits and possible risks of vaccination. (5.3)
the presentation) given by intramuscular injection (2.1):
------------------------------ ADVERSE REACTIONS ------------------------------
• Primary series: One dose each at 2, 4, and 6 months of age. The first dose
may be given as early as 6 weeks of age. Common solicited adverse reactions (≥20%) were pain and redness at the
injection site, irritability, drowsiness, fever, loss of appetite, fussiness, and
• Booster: One dose at 15 through 18 months of age.
restlessness. (6.1)
HIBERIX is supplied in 2 presentations:
• Vial and vial presentation: vial of Lyophilized Antigen Component and To report SUSPECTED ADVERSE REACTIONS, contact
vial of Sterile Saline Diluent. (2.2) GlaxoSmithKline at 1-888-825-5249 or VAERS at 1-800-822-7967 or
• Vial and prefilled syringe presentation: vial of Lyophilized Antigen www.vaers.hhs.gov.
Component and prefilled syringe of Sterile Saline Diluent. (2.2)
See 17 for PATIENT COUNSELING INFORMATION.
--------------------- DOSAGE FORMS AND STRENGTHS----------------------
Solution for injection. Revised: 12/2023
• Vial and vial presentation: a single dose after reconstitution is 0.5 mL. (3)

FULL PRESCRIBING INFORMATION: CONTENTS* 7 DRUG INTERACTIONS

FULL PRESCRIBING INFORMATION 7.1 Interference with Laboratory Tests
1 INDICATIONS AND USAGE 7.2 Concomitant Vaccine Administration
2 DOSAGE AND ADMINISTRATION 7.3 Immunosuppressive Therapies
2.1 Dose and Schedule 8 USE IN SPECIFIC POPULATIONS
2.2 Presentations and Reconstitution 8.4 Pediatric Use
2.3 Administration 11 DESCRIPTION
3 DOSAGE FORMS AND STRENGTHS 12 CLINICAL PHARMACOLOGY
4 CONTRAINDICATIONS 12.1 Mechanism of Action
5 WARNINGS AND PRECAUTIONS 13 NONCLINICAL TOXICOLOGY
5.1 Guillain-Barré Syndrome 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
5.2 Syncope 14 CLINICAL STUDIES
5.3 Apnea in Premature Infants 14.1 Immunological Evaluation
5.4 Preventing and Managing Allergic Vaccine Reactions 14.2 Concomitant Vaccine Administration
5.5 Altered Immunocompetence 15 REFERENCES
5.6 Interference with Laboratory Tests 16 HOW SUPPLIED/STORAGE AND HANDLING
5.7 Tetanus Immunization 16.1 Storage before Reconstitution
6 ADVERSE REACTIONS 17 PATIENT COUNSELING INFORMATION
6.1 Clinical Trials Experience
6.2 Postmarketing Experience *Sections or subsections omitted from the full prescribing information are not
listed.
______________________________________________________________________

1
FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

HIBERIX is indicated for active immunization for the prevention of invasive disease caused by
Haemophilus influenzae (H. influenzae) type b. HIBERIX is approved for use in children aged
6 weeks through 4 years (prior to fifth birthday).

2 DOSAGE AND ADMINISTRATION

For intramuscular use only.
2.1 Dose and Schedule
After reconstitution, a single dose of HIBERIX is either 0.5 mL or approximately 0.5 mL
depending on the presentation [see Dosage and Administration (2.2)].
HIBERIX is administered as a 4-dose series. The series consists of a primary immunization
course of 3 doses administered at 2, 4, and 6 months of age, followed by a booster dose
administered at 15 through 18 months of age. The first dose may be given as early as 6 weeks of
age.
2.2 Presentations and Reconstitution
HIBERIX is supplied in 2 presentations as follows:
Vial and Vial Presentation
The vial and vial presentation includes a vial of Lyophilized Antigen Component and a vial of
Sterile Saline Diluent.
Vial and Prefilled Syringe Presentation
The vial and prefilled syringe presentation includes a vial of Lyophilized Antigen Component
and a prefilled syringe of Sterile Saline Diluent.
For both presentations reconstitute the Lyophilized Antigen Component only with the
accompanying Sterile Saline Diluent to form HIBERIX.

2
Instructions for Vial and Vial Presentation

'
Sall~ ll~ru.lilUf~
Ollu~n v~ccine

;0.6ml t , o.5m
•
J Lyophilized
-l
• •
Antigen
Component

Figure 1. Cleanse both Figure 2. Transfer Figure 3. Shake Figure 4. After

vial stoppers. Using a 0.6 mL Sterile Saline the vial well reconstitution, withdraw
graduated syringe, Diluent into until the powder 0.5 mL of reconstituted
withdraw 0.6 mL of Lyophilized Antigen is completely vaccine into the same
Sterile Saline Diluent Component vial. dissolved. syringe and administer
from accompanying intramuscularly.
vial.

Instructions for Vial and Prefilled Syringe Presentation

Rci.:onstitutcd
Vaccin e

Saline
Diluent
■

Lyophilizcd
Anti gen
Component

Figure 1. Hold the Figure 2. Cleanse the Figure 3. Shake Figure 4. After
ungraduated prefilled syringe Lyophilized Antigen the vial well until reconstitution,
of Sterile Saline Diluent by Component vial stopper. the powder is withdraw the
the barrel and unscrew the Transfer the entire completely entire contents of
syringe cap by twisting it contents of the prefilled dissolved. reconstituted
counterclockwise. Align the syringe into the vial. vaccine into the
needle to the axis of the same syringe and
syringe and attach by gently after changing the
connecting the needle hub needle administer
into the Luer Lock Adaptor the vaccine
(LLA) and rotate a quarter intramuscularly.
turn clockwise until you feel
it lock.

3
2.3 Administration
The reconstituted vaccine should be a clear and colorless solution. Parenteral drug products
should be inspected visually for particulate matter and discoloration prior to administration,
whenever solution and container permit. If either of these conditions exists, the vaccine should
not be administered.
Administer HIBERIX intramuscularly immediately after reconstitution.

3 DOSAGE FORMS AND STRENGTHS

HIBERIX is a solution for injection.
For the vial and vial presentation a single dose after reconstitution is 0.5 mL.
For the vial and prefilled syringe presentation a single dose after reconstitution is approximately
0.5 mL.

4 CONTRAINDICATIONS
Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any H. influenzae type b- or
tetanus toxoid-containing vaccine or any component of the vaccine is a contraindication to
administration of HIBERIX [see Description (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Guillain-Barré Syndrome
If Guillain-Barré syndrome has occurred within 6 weeks of receipt of a prior vaccine containing
tetanus toxoid, the decision to give any tetanus toxoid-containing vaccine, including HIBERIX,
should be based on careful consideration of the potential benefits and possible risks.
5.2 Syncope
Syncope (fainting) can occur in association with administration of injectable vaccines, including
HIBERIX. Syncope can be accompanied by transient neurological signs such as visual
disturbance, paresthesia, and tonic-clonic limb movements. Procedures should be in place to
avoid falling injury and to restore cerebral perfusion following syncope.
5.3 Apnea in Premature Infants
Apnea following intramuscular vaccination has been observed in some infants born prematurely.
Decisions about when to administer an intramuscular vaccine, including HIBERIX, to infants
born prematurely should be based on consideration of the individual infant’s medical status, and
the potential benefits and possible risks of vaccination.
5.4 Preventing and Managing Allergic Vaccine Reactions
Prior to administration, the healthcare provider should review the patient's immunization history
for possible vaccine hypersensitivity. Epinephrine and other appropriate agents used for the

4
control of immediate allergic reactions must be immediately available should an acute
anaphylactic reaction occur.
5.5 Altered Immunocompetence
Safety and effectiveness of HIBERIX in immunosuppressed children have not been evaluated. If
HIBERIX is administered to immunosuppressed children, including children receiving
immunosuppressive therapy, the expected immune response may not be obtained.
5.6 Interference with Laboratory Tests
Urine antigen detection may not have a diagnostic value in suspected disease due to
H. influenzae type b within 1 to 2 weeks after receipt of a H. influenzae type b-containing
vaccine, including HIBERIX [see Drug Interactions (7.1)].
5.7 Tetanus Immunization
Immunization with HIBERIX does not substitute for routine tetanus immunization.

6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical
trials of another vaccine and may not reflect the rates observed in practice. There is the
possibility that broad use of HIBERIX could reveal adverse reactions not observed in clinical
trials.
Across clinical trials, common solicited adverse reactions (≥20%) were pain and redness at the
injection site, irritability, drowsiness, fever, loss of appetite, fussiness, and restlessness.
Study 1: In a randomized, controlled clinical trial conducted in the U.S., children were
vaccinated with HIBERIX (n = 2,963), a U.S.-licensed monovalent Haemophilus b Conjugate
Vaccine (Control PRP-T) (Sanofi Pasteur SA) (n = 520), or a U.S.-licensed combined Diphtheria
and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and
Haemophilus b Conjugate Vaccine (DTaP-IPV/Hib) (Sanofi Pasteur Ltd.) (n = 520) at 2, 4, and 6
months of age. HIBERIX and Control PRP-T (Sanofi Pasteur SA) were administered
concomitantly with PEDIARIX (DTaP-HBV-IPV) [Diphtheria and Tetanus Toxoids and
Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine]
and Pneumococcal 13-valent Conjugate Vaccine (PCV13) (Wyeth Pharmaceuticals Inc.) with
Doses 1, 2, and 3 and ROTARIX [Rotavirus Vaccine, Live, Oral] with Doses 1 and 2. DTaP-
IPV/Hib was administered concomitantly with PCV13 and ENGERIX-B [Hepatitis B Vaccine
(Recombinant)] with Doses 1, 2, and 3 and ROTARIX with Doses 1 and 2. If a birth dose of
hepatitis B vaccine was received, ENGERIX-B was given with Doses 1 and 3. In the total
population, 51.2% were male; 61% were white, 8% were Asian, 9% were black, and 22% were
other racial/ethnic groups.

5
In Study 1, children received a booster dose of either HIBERIX (n = 2,336), a Haemophilus b
Conjugate Vaccine (Control PRP-T) (Sanofi Pasteur SA) (n = 435), or a combined Diphtheria
and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and
Haemophilus b Conjugate Vaccine (DTaP-IPV/Hib) (Sanofi Pasteur Ltd.) (n = 400) at 15 to 18
months of age (mean age: 15.6 months) following primary vaccination at 2, 4, and 6 months of
age with the same vaccine. The booster dose of HIBERIX and Control PRP-T (Sanofi Pasteur
SA) was administered concomitantly with INFANRIX (DTaP) [Diphtheria and Tetanus Toxoids
and Acellular Pertussis Vaccine Adsorbed].
In 7 additional clinical studies, 1,008 children received HIBERIX as a booster dose following
primary vaccination with either HIBERIX (n = 530), Haemophilus b Conjugate Vaccine (Control
PRP-T) (Sanofi Pasteur SA) (n = 235), Haemophilus b Conjugate Vaccine (Merck & Co., Inc.)
(n = 26), or Haemophilus b Conjugate Vaccine (Wyeth Pharmaceuticals Inc.) (no longer licensed
in the U.S., n = 217). None of the studies included a comparator group that received a booster
dose with a U.S.-licensed Haemophilus b Conjugate Vaccine. Studies were conducted in Europe,
Canada, and Latin America. Across these studies, the mean age of subjects at the time of booster
vaccination with HIBERIX ranged from 16 to 19 months. At the time of vaccination, 172
(17.1%) subjects were aged 11 to 14 months, 642 (63.7%) subjects were aged 15 to 18 months,
and 194 (19.2%) subjects were aged 19 to 25 months. Approximately half of the subjects were
male. Among subjects for whom information on race/ethnicity was available, nearly all subjects
were white.
In these 7 studies, HIBERIX was administered concomitantly with non-U.S. formulations
(containing 2.5 mg 2-phenoxyethanol per dose as preservative) of one of the following U.S.-
licensed vaccines: INFANRIX (DTaP) [Diphtheria and Tetanus Toxoids and Acellular Pertussis
Vaccine Adsorbed], KINRIX (DTaP-IPV) [Diphtheria and Tetanus Toxoids and Acellular
Pertussis Adsorbed and Inactivated Poliovirus Vaccine], or PEDIARIX (DTaP-HBV-IPV). In the
studies, DTaP-IPV and DTaP-HBV-IPV were administered in dosing regimens not approved in
the U.S. Some subjects received DTaP-HBV (GlaxoSmithKline Biologicals, not licensed in
U.S.) concomitantly with HIBERIX.
Solicited Adverse Reactions
The reported frequencies of solicited local reactions and general adverse reactions from Study 1
after primary and booster vaccination are presented in Table 1 and Table 2, respectively.

6
Table 1. Percentage of Children with Solicited Local Reactions and General Adverse
Reactions within 4 Days of Primary Series Vaccinationa (at 2, 4, and 6 Months of Age) with
HIBERIXb, Control PRP-Tb, or DTaP-IPV/Hibc, Total Vaccinated Cohortd
HIBERIX Control PRP-T DTaP-IPV/Hib
% % %
Dose Dose Dose
Adverse Reactions 1 2 3 1 2 3 1 2 3
Local e

n 2,828 2,668 2,553 498 481 463 492 469 443

Pain 49 45 43 57 53 48 58 50 49
f
Pain, Grade 3 4 3 2 9 5 4 9 3 3
Redness 19 25 29 24 32 30 26 31 37
Redness, >20 mm 1 1 1 2 1 0 2 2 2
Swelling 13 15 19 19 22 20 20 24 24
Swelling, >20 mm 2 1 1 4 3 1 4 2 2
General
n 2,830 2,669 2,553 499 480 463 492 469 443
Irritability 69 70 67 76 71 67 73 67 69
g
Irritability, Grade 3 4 6 5 8 8 5 6 5 3
Drowsiness 60 54 49 66 56 50 61 52 50
h
Drowsiness, Grade 3 2 3 2 4 2 1 4 3 3
Loss of appetite 29 28 28 33 32 27 34 24 24
Loss of appetite, 1 2 2 2 1 0 1 0 1
i
Grade 3
Fever 14 19 19 16 19 16 12 11 18
j
Fever, Grade 3 0 1 1 0 0 1 0 0 1
n = All subjects for whom safety data were available.
a
Within 4 days of vaccination defined as day of vaccination and the next 3 days.
b
Each dose (Doses 1, 2, and 3) of HIBERIX or Control PRP-T (Sanofi Pasteur SA) was
concomitantly administered with PEDIARIX (DTaP-HBV-IPV) and PCV13. Doses 1 and 2
were concomitantly administered with ROTARIX.
c
Each dose (Doses 1, 2, and 3) of DTaP-IPV/Hib was concomitantly administered with PCV13
and ENGERIX-B with Doses 1, 2, and 3 and ROTARIX with Doses 1 and 2. If a birth dose of
hepatitis B vaccine was received, ENGERIX-B was given with Doses 1 and 3.
d
Study 1: NCT01000974.
e
Local reactions at the injection site for HIBERIX, Control PRP-T, or DTaP-IPV/Hib.
f
Grade 3 pain defined as cried when limb was moved/spontaneously painful.
g
Grade 3 irritability defined as crying that could not be comforted/prevented normal activity.
h
Grade 3 drowsiness defined as prevented normal daily activity.
i
Grade 3 loss of appetite defined as did not eat at all.
j
Fever defined as ≥100.4°F (≥38.0°C) rectally; Grade 3 fever defined as >103.1°F (>39.5°C)
rectally.

7
Table 2. Percentage of Children with Solicited Local Reactions and General Adverse
Reactions within 4 Days of Booster Vaccinationa (Dose 4 at 15 through 18 Months of Age)
with HIBERIXb, Control PRP-Tb, or DTaP-IPV/Hib, Total Vaccinated Cohortc
HIBERIX Control PRP-T DTaP-IPV/Hib%
% %
Adverse Reactions Any Grade 3d Any Grade 3d Any I Grade 3d
Locale n = 2,224 n = 416 n = 379
Pain 41 1 43 1 43 2
Redness 30 0 31 1 30 3
Swelling 18 1 20 1 20 3
General n = 2,225 n = 416 n = 379
Irritability 58 2 60 5 53 2
Drowsiness 39 1 39 3 31 0
Loss of appetite 28 1 34 2 22 1
f
Fever 15 1 14 1 18 1
n = All subjects for whom safety data were available.
Subjects received primary vaccination at 2, 4, and 6 months of age with the same vaccine as the
booster dose.
a
Within 4 days of vaccination defined as day of vaccination and the next 3 days.
b
The booster dose of HIBERIX and Control PRP-T (Sanofi Pasteur SA) was concomitantly
administered with INFANRIX (DTaP).
c
Study 1: NCT01000974.
d
Grade 3 pain defined as cried when limb was moved/spontaneously painful.
Grade 3 redness, swelling defined as >20 mm.
Grade 3 irritability defined as crying that could not be comforted/prevented normal activity.
Grade 3 drowsiness defined as prevented normal daily activity.
Grade 3 loss of appetite defined as did not eat at all.
Grade 3 fever defined as >102.2°F (>39.0°C) axillary.
e
Local reactions at the injection site for HIBERIX, Control PRP-T, or DTaP-IPV/Hib.
f
Fever defined as ≥99.5°F (≥37.5°C) axillary.
In an open-label, multicenter study conducted in Germany (Study 2), 371 children received a
booster dose of HIBERIX administered concomitantly with DTaP-HBV-IPV. The mean age at
the time of vaccination was 16 months. Subjects in this study had previously received a primary
series with either HIBERIX (n = 92), Control PRP-T (Sanofi Pasteur SA) (n = 96), or
Haemophilus b Conjugate Vaccine (Wyeth Pharmaceuticals Inc.) (no longer licensed in the U.S.)
(n = 183). All subjects previously received 3 doses of DTaP-HBV-IPV. The reported frequencies
of solicited local reactions and general adverse reactions are presented in Table 3.

8
Table 3. Percentage of Children with Solicited Local Reactions and General Adverse
Reactions within 4 Days of Booster Vaccinationa (Dose 4) with HIBERIXb Coadministered
with DTaP-HBV-IPVc, Intent-to-Treat Cohort (n = 371)
% %
Adverse Reactions Any Grade 3
Locald
Redness 25 2e
Pain 21 1f
Swelling 15 2e
General
Feverg 35 4
Fussiness 26 1h
Loss of appetite 23 1i
Restlessness 22 1i
Sleepiness 20 1i
Diarrhea 15 1i
Vomiting 5 1i
n = All subjects for whom safety data were available.
a
Within 4 days of vaccination defined as day of vaccination and the next 3 days.
b
In this study, 92 subjects previously received 3 doses of HIBERIX, 96 subjects previously
received 3 doses of a Control PRP-T (Sanofi Pasteur SA), and 183 subjects previously received
3 doses of a Haemophilus b Conjugate Vaccine that is no longer licensed in the U.S.
c
In this study, DTaP-HBV-IPV was given to subjects who previously received 3 doses of DTaP-
HBV-IPV. In the U.S., PEDIARIX is approved for use as a 3-dose primary series; use as a
fourth consecutive dose is not approved in the U.S.
d
Local reactions at the injection site for HIBERIX.
e
Grade 3 redness or swelling defined as >20 mm.
f
Grade 3 pain defined as causing crying when limb moved.
g
Fever defined as ≥100.4°F (≥38.0°C) rectally or ≥99.5°F (≥37.5°C) axillary, oral, or tympanic;
Grade 3 fever defined as >103.1°F (>39.5°C) rectally or >102.2°F (>39.0°C) axillary, oral, or
tympanic.
h
Grade 3 fussiness defined as persistent crying and could not be comforted.
i
Grade 3 for these symptoms defined as preventing normal daily activity.

Serious Adverse Reactions

In Study 1, one of 2,963 subjects who received HIBERIX and coadministered vaccines given at
2, 4, and 6 months of age experienced a serious adverse reaction which was in temporal
association with vaccination and had no alternative plausible causes (convulsion on Day 14 after
Dose 1). One of 2,336 subjects who received a booster dose of HIBERIX concomitantly with
INFANRIX experienced a serious adverse reaction which was in temporal association with

9
vaccination and had no alternative plausible causes (new onset febrile seizure on Day 1 after
Dose 4).
In the 7 additional studies, 2 of 1,008 subjects reported a serious adverse reaction that occurred
in the 31-day period following booster immunization with HIBERIX. One subject developed
bilateral pneumonia 9 days post-vaccination and one subject experienced asthenia following
accidental drug ingestion 18 days post-vaccination.
6.2 Postmarketing Experience
In addition to reports in clinical trials for HIBERIX, the following adverse reactions have been
identified during postapproval use of HIBERIX. Because these reactions are reported voluntarily
from a population of uncertain size, it is not possible to reliably estimate their frequency or
establish a causal relationship to vaccination.
General Disorders and Administration Site Conditions
Extensive swelling of the vaccinated limb, injection site induration.
Immune System Disorders
Allergic reactions (including anaphylactic and anaphylactoid reactions), angioedema.
Nervous System Disorders
Convulsions (with or without fever), hypotonic-hyporesponsive episode (i.e., sudden onset of
hypotonia, hyporesponsiveness, and pallor or cyanosis), somnolence, syncope, or vasovagal
responses to injection.
Respiratory, Thoracic, and Mediastinal Disorders
Apnea [see Warnings and Precautions (5.3)].
Skin and Subcutaneous Tissue Disorders
Rash, urticaria.

7 DRUG INTERACTIONS
7.1 Interference with Laboratory Tests
Haemophilus b capsular polysaccharide derived from Haemophilus b Conjugate Vaccines has
been detected in the urine of some vaccinees.1 Urine antigen detection may not have a diagnostic
value in suspected disease due to H. influenzae type b within 1 to 2 weeks after receipt of a
H. influenzae type b-containing vaccine, including HIBERIX [see Warnings and Precautions
(5.6)].
7.2 Concomitant Vaccine Administration
In clinical studies, HIBERIX was administered concomitantly with routinely recommended
pediatric vaccines [see Clinical Studies (14.2)].

10
7.3 Immunosuppressive Therapies
Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic
drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune
response to HIBERIX.

8 USE IN SPECIFIC POPULATIONS

8.4 Pediatric Use
Safety and effectiveness of HIBERIX in children younger than 6 weeks and in children aged 5 to
16 years have not been established.

11 DESCRIPTION
HIBERIX [Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)] is a solution for
intramuscular injection, supplied as a sterile, lyophilized powder which is reconstituted at the
time of use with the accompanying saline diluent. HIBERIX contains Haemophilus b capsular
polysaccharide (polyribosyl-ribitol-phosphate [PRP]), a high molecular weight polymer prepared
from the H. influenzae type b strain 20,752 grown in a synthetic medium that undergoes heat
inactivation and purification. The tetanus toxin, prepared from Clostridium tetani grown in a
semi-synthetic medium, is detoxified with formaldehyde and purified. The capsular
polysaccharide is covalently bound to the tetanus toxoid. After purification, the conjugate is
lyophilized in the presence of lactose as a stabilizer. The diluent for HIBERIX is a sterile saline
solution (0.9% sodium chloride) supplied in vials or prefilled syringes.
After reconstitution, each approximately 0.5-mL dose of HIBERIX contains 10 mcg of purified
capsular polysaccharide conjugated to approximately 25 mcg of tetanus toxoid, 12.6 mg of
lactose, and ≤0.5 mcg of residual formaldehyde.
HIBERIX does not contain a preservative.
The stopper of the vial containing Lyophilized Antigen Component or Sterile Saline Diluent and
the tip cap and rubber plunger stopper of the prefilled syringe containing Sterile Saline Diluent
are not made with natural rubber latex.

12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
H. influenzae is a gram-negative coccobacillus. Most strains of H. influenzae that cause invasive
disease are type b. H. influenzae type b can cause invasive disease such as sepsis and meningitis.
Specific levels of antibodies to polyribosyl-ribitol-phosphate (anti-PRP) have been shown to
correlate with protection against invasive disease due to H. influenzae type b. Based on data from
passive antibody studies2 and a clinical efficacy study with unconjugated Haemophilus b
polysaccharide vaccine3, an anti-PRP concentration of 0.15 mcg/mL has been accepted as a

11
minimal protective level. Data from an efficacy study with unconjugated Haemophilus b
polysaccharide vaccine indicate that an anti-PRP concentration of ≥1.0 mcg/mL predicts
protection through at least a 1-year period.4,5 These antibody levels have been used to evaluate
the effectiveness of Haemophilus b Conjugate Vaccines, including HIBERIX.

13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
HIBERIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of
fertility.

14 CLINICAL STUDIES
14.1 Immunological Evaluation
Primary Series Vaccination (Doses 1, 2, and 3)
The immunogenicity of HIBERIX was evaluated in a randomized, controlled trial (Study 1).
HIBERIX or control vaccines were administered concomitantly with U.S.-licensed vaccines [see
Adverse Reactions (6.1)].
Anti-PRP geometric mean concentrations (GMCs) and seroprotection rates 1 month following
Dose 3 of HIBERIX, Control PRP-T (Sanofi Pasteur SA), or DTaP-IPV/Hib are presented in
Table 4.

12
Table 4. Anti-PRP GMCs and Seroprotection Rates 1 Month following 3 Doses of
HIBERIX, Control PRP-Ta, or DTaP-IPV/Hibb Administered at 2, 4, and 6 Months of
Age, ATP Cohort for Immunogenicityc
Anti-PRP GMC % Anti-PRP % Anti-PRP
(mcg/mL) ≥0.15 mcg/mL ≥1.0 mcg/mL
Vaccine n (95% CI) (95% CI) (95% CI)
HIBERIX 1,590 5.19 96.6 81.2
(4.77, 5.66) (95.6, 97.4) (79.2, 83.1)
Control PRP-T 274 6.74 96.7d 89.8e
(5.59, 8.13) (93.9, 98.5) (85.6, 93.1)
DTaP-IPV/Hib 253 3.64 92.5f 78.3f
(2.89, 4.58) (88.5, 95.4) (72.7, 83.2)
a
U.S.-licensed monovalent Haemophilus b Conjugate Vaccine (Control PRP-T) (Sanofi Pasteur
SA).
b
U.S.-licensed DTaP-IPV/Hib Vaccine (Sanofi Pasteur Ltd.).
c
Study 1: NCT01000974.
d
HIBERIX was non-inferior to Control PRP-T for percent of subjects achieving anti-PRP
≥0.15 mcg/mL (lower limit of 95% CI on difference of HIBERIX minus Control PRP-T ≥
predefined limit of -5%).
e
The non-inferiority criterion was not met (lower limit of 95% CI for the difference in the
percentages of subjects with anti-PRP ≥1.0 mcg/mL between two groups [HIBERIX minus
Control PRP-T] was -12.28%, which was lower than the predefined limit of -10%).
f
Analyses of anti-PRP immune responses following DTaP-IPV/Hib vaccination were
exploratory.

Booster Vaccination (Dose 4)

The immunogenicity of HIBERIX administered as a booster dose at 15 to 18 months of age was
evaluated in a subset of children from Study 1 (n = 336) in comparison with U.S.-licensed
vaccines following primary vaccination at 2, 4, and 6 months of age [see Adverse Reactions
(6.1)]. The booster dose of HIBERIX and Control PRP-T (Sanofi Pasteur SA) was administered
concomitantly with INFANRIX.
Antibodies to PRP were measured in sera obtained immediately prior to and 1 month after
booster vaccination with HIBERIX or the control vaccines. Anti-PRP GMCs and seroprotection
rates are presented in Table 5.

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Table 5. Anti-PRP GMCs and Seroprotection Rates prior to and 1 Month following a
Booster Dose (Dose 4 at 15 through 18 Months of Age) of HIBERIX, Control PRP-Ta, or
DTaP-IPV/Hibb, ATP Cohort for Immunogenicityc
Anti-PRP GMC % Anti-PRP % Anti-PRP
(mcg/mL) ≥0.15 mcg/mL ≥1.0 mcg/mL
(95% CI) (95% CI) (95% CI)
Vaccine n Pre- Post- Pre- Post- Pre- Post-
HIBERIX 329-336 0.50 48.78 75.1 100.0 32.2 99.1
(0.42, 0.59) (42.0, 56.66) (70.0, 79.7) (98.9, 100.0) (27.2, 37.6) (97.4, 99.8)
Control PRP-T 226-236 0.47 40.29 76.1 99.6 27.0 97.9d
(0.38, 0.57) (33.39, 48.63) (70.0, 81.5) (97.7, 100.0) (21.3, 33.3) (95.1, 99.3)
DTaP-IPV/Hib 175-186 0.38 37.54 66.3 100.0 25.1 98.9e
(0.30, 0.48) (30.53, 46.16) (58.8, 73.2) (98.0, 100.0) (18.9, 32.2) (96.2, 99.9)
a
U.S.-licensed monovalent Haemophilus b Conjugate Vaccine (Control PRP-T) (Sanofi Pasteur
SA).
b
U.S.-licensed DTaP-IPV/Hib Vaccine (Sanofi Pasteur Ltd.).
c
Study 1: NCT01000974.
d
HIBERIX was non-inferior to Control PRP-T for percent of subjects achieving anti-PRP
≥1.0 mcg/mL (lower limit of 97.5% CI on difference of HIBERIX minus Control PRP-T
≥predefined limit of -10%) at 1 month following the booster dose.
e
Analyses of anti-PRP immune responses following DTaP-IPV/Hib vaccination were
exploratory.

In 6 additional clinical studies, the immune response to HIBERIX administered as a booster dose
was evaluated in a total of 415 children aged 12 to 23 months. At the time of vaccination, 30
children were aged 12 to 14 months, 316 children were aged 15 to 18 months, and 69 children
were aged 19 to 23 months. Among subjects, 43% to 60% were male. Among subjects for whom
information on race/ethnicity was available, nearly all subjects were white. None of the studies
included a comparator group that received a booster dose with a U.S.-licensed Haemophilus b
Conjugate Vaccine. Characteristics of 3 of these studies are presented in Table 6.

14
Table 6. Characteristics of 3 Open-Label Booster Immunization Studies of HIBERIX
Booster Vaccination with
Per-Protocol HIBERIX
Immunogenicity Age at Concomitantly
Cohort Vaccination Administered
Study Country n Priming History (months) Vaccinea
3 Canada 42 DTaP-HBV-IPVb + 16-18 DTaP-HBV-
Haemophilus b IPVb
Conjugate Vaccinec
at 2, 4, and 6 months
of age
4 Canada 64 DTaP-IPVd + 16-19 DTaP-IPVd
HIBERIX
at 2, 4, and 6 months
of age
5 Germany 108 DTaP-HBVe + 16-23 DTaP-HBVe
HIBERIX
at 3, 4, and 5 months
of age
a
Administered at a separate site.
b
Non-U.S. formulation equivalent to PEDIARIX with the exception of containing 2.5 mg 2-
phenoxyethanol per dose as preservative. In the U.S., PEDIARIX is approved for use as a 3-
dose primary series; use as a fourth consecutive dose is not approved in the U.S.
c
U.S.-licensed Haemophilus b Conjugate Vaccine (Control PRP-T) (Sanofi Pasteur SA).
d
Non-U.S. formulation equivalent to KINRIX with the exception of containing 2.5 mg 2-
phenoxyethanol per dose as preservative. In the U.S., KINRIX is approved for use as the fifth
dose of DTaP and the fourth dose of IPV in children aged 4 to 6 years previously primed with
approved dosing regimens of INFANRIX and/or PEDIARIX. The DTaP-IPV dosing regimen is
not approved in the U.S.
e
Manufactured by GlaxoSmithKline Biologicals (not licensed in the U.S.).

Antibodies to PRP were measured in sera obtained immediately prior to and 1 month after
booster vaccination with HIBERIX. Geometric mean concentrations and anti-PRP seroprotection
rates are presented in Table 7.

15
Table 7. Anti-PRP GMCs and Seroprotection Rates prior to and 1 Month following a
Booster Dose of HIBERIX, Per-Protocol Immunogenicity Cohort
Anti-PRP GMC % Anti-PRP % Anti-PRP
(mcg/mL) ≥0.15 mcg/mL ≥1.0 mcg/mL
Study n Pre- Post- Pre- Post- Pre- Post-
3a 42 0.46 59.07 76.2 100 35.7 97.6
b
4 63-64 0.25 47.78 71.4 100 12.7 100
5c 108 0.59 96.12 77.8 100 32.4 100
GMC = Geometric mean antibody concentration.
n = Number of children for whom serological results were available for the pre- and post-dose
immunological evaluations.
Studies 3, 4, and 5 correspond to Studies 3, 4, and 5, respectively in Table 6.
a
Canadian study in children aged 16 to 18 months who previously received 3 doses of DTaP-
HBV-IPV and Haemophilus b Conjugate Vaccine (Control PRP-T) (Sanofi Pasteur SA). The
booster dose of HIBERIX was coadministered with DTaP-HBV-IPV (a fourth consecutive dose
of PEDIARIX is not approved in the U.S.). In this study, pre-vaccination sera may have been
obtained up to 1 week prior to booster vaccination with HIBERIX.
b
Canadian study in children aged 16 to 19 months who previously received 3 doses of DTaP-
IPV and HIBERIX. The booster dose of HIBERIX was coadministered with DTaP-IPV. The
DTaP-IPV dosing regimen is not approved in the U.S.
c
German study in children aged 16 to 23 months who previously received 3 doses of DTaP-
HBV (GlaxoSmithKline Biologicals, not licensed in the U.S.) and HIBERIX. The booster dose
of HIBERIX was coadministered with DTaP-HBV.

14.2 Concomitant Vaccine Administration

Primary Series Vaccination (Doses 1, 2, and 3)
In U.S. Study 1, subjects who received HIBERIX concomitantly with PEDIARIX (DTaP-HBV-
IPV) and PCV13 at 2, 4, and 6 months of age had no evidence for reduced antibody responses
relative to the response in control subjects administered Control PRP-T (Sanofi Pasteur SA)
concomitantly with PEDIARIX (DTaP-HBV-IPV) and PCV13, to pertussis antigens (GMC to
pertussis toxin, filamentous hemagglutinin, and pertactin), diphtheria toxoid (antibody levels
≥0.1 IU/mL), tetanus toxoid (antibody levels ≥0.1 IU/mL), poliovirus types 1, 2, and 3 (antibody
levels ≥1:8 to each virus), PCV13 (antibody levels ≥0.2 mcg/mL and GMC to each serotype), or
hepatitis B (anti-hepatitis B surface antigen ≥10 mIU/mL). The immune responses to PEDIARIX
(DTaP-HBV-IPV) and PCV13 were evaluated 1 month following Dose 3. Subjects in both
groups received ROTARIX at 2 and 4 months of age.
Booster Vaccination (Dose 4)
In U.S. Study 1, subjects who received a booster dose of HIBERIX concomitantly with
INFANRIX at 15 to 18 months of age had no evidence for reduced antibody responses to

16
pertussis antigens (GMC to pertussis toxin, filamentous hemagglutinin, and pertactin), diphtheria
toxoid (antibody levels ≥0.1 IU/mL), and tetanus toxoid (antibody levels ≥0.1 IU/mL), relative to
the responses in control subjects administered Control PRP-T (Sanofi Pasteur SA) concomitantly
with INFANRIX.
In 7 additional studies, a booster dose of HIBERIX was administered concomitantly with non-
U.S. formulations of INFANRIX, KINRIX, and PEDIARIX. Non-U.S. formulations of KINRIX
and PEDIARIX were administered in dosing regimens not approved in the U.S.
Sufficient data are not available to confirm lack of interference in immune responses to vaccines
other than INFANRIX administered concomitantly with a booster dose of HIBERIX.

15 REFERENCES
1. Rothstein EP, Madore DV, Girone JAC, et al. Comparison of antigenuria after immunization
with three Haemophilus influenzae type b conjugate vaccines. Pediatr Infect Dis J.
1991;10:311-314.
2. Robbins JB, Parke JC, Schneerson R, et al. Quantitative measurement of “natural” and
immunization-induced Haemophilus influenzae type b capsular polysaccharide antibodies.
Pediatr Res. 1973;7:103-110.
3. Peltola H, Käythy H, Sivonen A, et al. Haemophilus influenzae type b capsular
polysaccharide vaccine in children: A double-blind field study of 100,000 vaccinees
3 months to 5 years of age in Finland. Pediatrics. 1977;60:730-737.
4. Käythy H, Peltola H, Karanko V, et al. The protective level of serum antibodies to the
capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis. 1983;147:1100.
5. Anderson P. The protective level of serum antibodies to the capsular polysaccharide of
Haemophilus influenzae type b. J Infect Dis. 1984;149:1034.

16 HOW SUPPLIED/STORAGE AND HANDLING

HIBERIX Vial and Vial presentation is supplied in a carton packaged without syringes or
needles (NDC 58160-818-11) containing:
• 10 single-dose vials of Lyophilized Antigen Component (NDC 58160-816-01) in a carton:
NDC 58160-816-05.
• 10 single-dose vials of Sterile Saline Diluent (NDC 58160-817-01) in a carton: NDC 58160-
817-05.
HIBERIX Vial and Prefilled Syringe Presentation is supplied in a carton (NDC 58160-726-15)
containing:
• 10 single-dose vials of Lyophilized Antigen Component: NDC 58160-816-03.

17
• 10 single-dose, prefilled, ungraduated TIP-LOK syringes (Luer Lock syringes) of Sterile
Saline Diluent packaged without needles NDC 58160-817-02.
TIP-LOK syringes are to be used with Luer Lock compatible needles.
The stopper of the vial containing Lyophilized Antigen Component or Sterile Saline Diluent and
the tip cap and rubber plunger stopper of the prefilled syringe containing Sterile Saline Diluent
are not made with natural rubber latex.
16.1 Storage before Reconstitution
Lyophilized Antigen Component vials: Store refrigerated between 2° and 8°C (36° and 46°F).
Protect vials from light.
Sterile Saline Diluent prefilled syringes and vials: Store refrigerated or at controlled room
temperature between 2° and 25°C (36° and 77°F). Do not freeze. Discard if the diluent has been
frozen.
17 PATIENT COUNSELING INFORMATION
• Inform parents or guardians of the potential benefits and risks of immunization with
HIBERIX.
• Inform parents or guardians about the potential for adverse reactions that have been
temporally associated with administration of HIBERIX or other vaccines containing similar
components.
• Give parents or guardians the Vaccine Information Statements, which are required by the
National Childhood Vaccine Injury Act of 1986 to be given prior to immunization. These
materials are available free of charge at the Centers for Disease Control and Prevention
(CDC) website (www.cdc.gov/vaccines).
Trademarks are owned by or licensed to the GSK group of companies.
Manufactured by GlaxoSmithKline Biologicals
Rixensart, Belgium, U.S. License 1617, and
Distributed by GlaxoSmithKline
Durham, NC 27701
18
©2023 GSK group of companies or its licensor.
HRX:9PI

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