Product Monograph - Avaxim - Pediatric -(5mL Vial)
SUMMARY PRODUCT INFORMATION
Route of Administration
Intramuscular injection.
Dosage Form/Strength
Suspension for injection.
Each 0.5 mL dose is formulated to contain:
Active Ingredients
Hepatitis A virus Inactivated (GBM strain) – 80 antigen units (U)
Clinically Relevant Non-medicinal Ingredients
Excipients: 2-phenoxyethanol, formaldehyde, aluminum hydroxide (expressed as aluminum), Medium 199 Hanks, polysorbate 80.
Manufacturing process residuals: neomycin.
For a complete listing see DOSAGE FORMS, COMPOSITION AND PACKAGING.
DESCRIPTION
AVAXIM® - Pediatric [Hepatitis A Vaccine Inactivated] is a sterile, whitish, cloudy suspension. The active ingredient is a purified and formaldehyde-inactivated hepatitis A virus (HAV) obtained from the GBM strain, cultured on MRC-5 human diploid cells. HAV is adsorbed onto aluminum.
INDICATIONS AND CLINICAL USE
AVAXIM® - Pediatric is indicated for active immunization against infection caused by HAV in persons 12 months to 15 years of age inclusive. AVAXIM® - Pediatric can be used for primary immunization or as a booster following primary immunization with AVAXIM® - Pediatric or other similar hepatitis A vaccines. (1) (2) (3)
Please refer to the National Advisory Committee on Immunization (NACI) and the Canadian Immunization Guide for current recommendations on the use of hepatitis A vaccines in Canada. (1)
Pediatrics
AVAXIM® - Pediatric is not indicated for immunization of persons under the age of 12 months or persons 16 years of age and older.
CONTRAINDICATIONS
Hypersensitivity
Known systemic hypersensitivity reaction to any component of AVAXIM® - Pediatric or a life-threatening reaction after previous administration of the vaccine or a vaccine containing one or more of the same components are contraindications to vaccination. (1) (See SUMMARY PRODUCT INFORMATION.)
WARNINGS AND PRECAUTIONS
General
Before administration of AVAXIM® - Pediatric, health-care providers should inform the recipient or the parent or guardian of the recipient of the benefits and risks of immunization, inquire about the recent health status of the recipient, review the recipient’s history concerning possible hypersensitivity to the vaccine or similar vaccine, previous immunization history, the presence of any contraindications to immunization and comply with any local requirements with respect to information to be provided to the recipient, parent or guardian before immunization.
Because of the incubation period of hepatitis A disease, infection may be present but not clinically apparent at the time of vaccination. It is not known whether AVAXIM® - Pediatric will prevent hepatitis A in this case.
Seropositivity against HAV is not a contraindication. (4)
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent falling injury and manage syncopal reactions.
Administration Route-Related Precautions: Do not administer AVAXIM® - Pediatric by intravascular injection. Do not administer intradermally.
AVAXIM® - Pediatric should not be administered into the buttocks.
Febrile or Acute Disease: Vaccination should be postponed in cases of an acute or febrile disease. (5) However, a disease with a low-grade fever should not usually be a reason to postpone vaccination.
Protection
AVAXIM® - Pediatric does not provide protection against infection caused by hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, or by other liver pathogens, other than HAV.
As with any vaccine, AVAXIM® - Pediatric may not protect 100% of vaccinated individuals.
Hematologic
Because any intramuscular injection can cause an injection site hematoma in persons with any bleeding disorders, such as hemophilia or thrombocytopenia, or in persons on anticoagulant therapy, intramuscular injections with AVAXIM® - Pediatric should not be administered to such persons unless the potential benefits outweigh the risk of administration. If the decision is made to administer any product by intramuscular injection to such persons, it should be given with caution, with steps taken to avoid the risk of hematoma formation following injection.
In exceptional circumstances (e.g., in patients with thrombocytopenia or in patients at risk of hemorrhage), the vaccine may be administered by the subcutaneous route, however, this may be associated with a higher risk of local reaction including injection site nodule. (6) (7)
Immune
The possibility of allergic reactions in persons sensitive to components of the vaccine should be evaluated. Hypersensitivity reactions may occur following the use of AVAXIM® - Pediatric even in persons with no prior history of hypersensitivity to the product components. (See DOSAGE FORMS, COMPOSITION AND PACKAGING.)
As with all other products, epinephrine hydrochloride solution (1:1,000) and other appropriate agents should be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs. (8) Health-care providers should be familiar with current recommendations for the initial management of anaphylaxis in non-hospital settings, including proper airway management. (8) For instructions on recognition and treatment of anaphylactic reactions, see the current edition of the Canadian Immunization Guide or visit the Health Canada website.
Immunocompromised persons (whether from disease or treatment) may not obtain the expected immune response. If possible, consideration should be given to delaying vaccination until after the completion of any immunosuppressive treatment. (9) Nevertheless, vaccination of persons with chronic immunodeficiency such as HIV infection is recommended even if the antibody response might be limited. (9) (5)
Pregnant Women
Animal reproduction studies have not been conducted with AVAXIM® - Pediatric.
Data on the use of this vaccine in pregnant woman are limited. Therefore, the administration of the vaccine during pregnancy is not recommended. AVAXIM® - Pediatric should be given to pregnant women only if clearly needed, and following an assessment of its risks and benefits.
Nursing Women
It is not known whether this vaccine is excreted in human milk. Caution must be exercised when AVAXIM® - Pediatric is administered to a nursing mother.
ADVERSE REACTIONS
Clinical Trial Adverse Reactions
Because clinical trials are conducted under very specific conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect rates observed in practice. The adverse reaction information from clinical trials does however, provide a basis for identifying the adverse events that appear to be related to vaccine use and for approximating rates of those events.
More than 6,200 children aged 12 months to 15 years were vaccinated with AVAXIM® - Pediatric during clinical trials. A pooled analysis was performed by integrating data from 5,458 subjects included in 15 clinical trials conducted between 1996 and 2014, who received at least one dose of AVAXIM® - Pediatric. The mean age of the subjects was 5.80 years (ranging from 11.8 months to 16.0 years) at the time of the first injection, and 6.69 years (ranging from 17.2 months to 16.8 years) at the second injection. The proportion of male and female subjects was balanced with 51.4% male subjects. The subjects were from 12 countries in Europe, Asia and Latin America.
Table 1 summarizes the percentage of subjects from this pooled analysis experiencing at least one solicited adverse reaction within 7 days post-vaccination with AVAXIM® - Pediatric.
Table 1: Solicited Adverse Reactions Within 7 Days Following AVAXIM ® - Pediatric (6)
| Adverse Reaction | After the First Dose (%)⃰ N† = 5,458 | After the Second Dose (%)⃰ N† = 4,777 |
| Injection site reaction | ||
| Injection site pain | 13.4 | 9.8 |
| Injection site erythema | 4.6 | 2.3 |
| Injection site induration/oedema | 2.5 | 1.3 |
| Injection site haematoma | 1.5 | 0.7 |
| Systemic Reaction | ||
| Crying abnormal | 13.0 | 0.9 |
| Malaise | 8.9 | 6.3 |
| Headache | 8.6 | 4.6 |
| Myalgia | 6.7 | 4.7 |
| Decreased appetite | 6.1 | 2.2 |
| Pyrexia | 5.5 | 2.4 |
| Irritability | 5.1 | 1.4 |
| Abdominal pain | 4.6 | 2.4 |
| Asthenia/Drowsiness | 4.5 | 1.4 |
| Diarrhea | 3.6 | 1.6 |
| Vomiting | 3.5 | 1.4 |
| Nausea | 3.0 | 1.0 |
| Arthralgia | 1.8 | 0.8 |
| Insomnia | 1.7 | 1.0 |
| Urticaria | 0.9 | 0.0 |
| Rash | 0.0 | 0.5 |
⃰ For each reaction, the frequency has been defined by the number of subjects experiencing the reaction divided by the number of subjects with available data; the number of subjects with available data ranges from 50 to 5,353.
† N: the number of subjects who received AVAXIM® - Pediatric.
In subjects seropositive against HAV, AVAXIM® - Pediatric, was as well tolerated as in seronegative subjects.
Post-Market Adverse Reactions
The following additional adverse reactions have been spontaneously reported during the post-marketing use of AVAXIM® - Pediatric. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Decisions to include these events in labelling were based on one or more of the following factors: 1) severity of the events, 2) frequency of reporting, or 3) strength of causal connection to AVAXIM® - Pediatric.
Nervous system disorders
Vasovagal syncope
Physicians, nurses and pharmacists should report any adverse occurrences temporally related to the administration of the product in accordance with local requirements and to the Pharmacovigilance Department, Sanofi Canada, 2905 Place Louis-R-Renaud, Laval, QC, H7V 0A3 Canada. 1-888-621-1146 (phone).
DRUG INTERACTIONS
Vaccine-Drug Interactions
Immunosuppressive treatments may interfere with the development of the expected immune response. (See WARNINGS AND PRECAUTIONS.) No interaction with other medication is currently known.
Concomitant Vaccine Administration
AVAXIM® - Pediatric may be administered simultaneously with immune globulin at separate sites with separate syringes. Seroconversion rates are not modified, but antibody titres could be lower than after vaccination with the vaccine alone. (10)
As the vaccine is inactivated, concomitant administration of other vaccine(s) given at other injection sites is unlikely to interfere with immune responses.
AVAXIM® - Pediatric may be administered concomitantly with trivalent live attenuated vaccine for combined immunization against measles, mumps and rubella (MMR). (11) (12)
Vaccines administered simultaneously must be given using separate syringes at separate sites.
AVAXIM® - Pediatric should not be mixed in the same syringe with other parenterals.
DOSAGE AND ADMINISTRATION
Recommended Dose
Primary immunization:
AVAXIM® - Pediatric should be administered as a single dose injection (0.5 mL) by the intramuscular route.
Booster immunization:
After primary vaccination, a booster dose of 0.5 mL is recommended in order to confer long-term protection. This booster dose should be given preferably 6 months to 36 months after the primary vaccination, but can be given up to 7 years after primary vaccination.
The need for another booster dose is not fully established. However, long-term antibody persistence data showed that anti-HAV antibodies persist up to 14-15 years in healthy individuals after a two-dose vaccination schedule with AVAXIM® - Pediatric (See Duration of Effect).
Administration
Inspect for extraneous particulate matter and/or discolouration before use. (See DESCRIPTION.) If these conditions exist, the product should not be administered.
Shake the pre-filled syringe well until a uniform, cloudy suspension results.
AVAXIM® - Pediatric may be packaged in one of three presentations: a pre-filled syringe with a choice of two needles, a pre-filled syringe with attached needle, or a 10 dose vial.
If two needles are present, select a needle of appropriate length to ensure that the vaccine will be delivered intramuscularly. Remove the tip cap from the syringe, take the chosen needle from the blister pack and fix to the tip of the pre-filled syringe.
If a syringe with attached needle is present, the vaccine is ready to administer.
Use a separate sterile needle and syringe, or a sterile disposable unit for each individual patient to prevent disease transmission. When administering a dose from a stoppered vial, do not remove either the stopper or the metal seal holding it in place. Aseptic technique must be used for withdrawal of each dose. Needles should not be recapped and should be disposed of according to biohazard waste guidelines.
Administer the vaccine intramuscularly (I.M.). The preferred site of injection is the deltoid muscle.
Give the patient a permanent personal immunization record. In addition, it is essential that the physician or nurse record the immunization history in the permanent medical record of each patient. This permanent office record should contain the name of the vaccine, date given, dose, manufacturer and lot number.
OVERDOSAGE
For management of a suspected drug overdose, contact your regional Poison Control Centre.
ACTION AND CLINICAL PHARMACOLOGY
HAV is a single serotype, ribonucleic acid (RNA) virus of the Picornaviridae family. HAV is transmitted via the fecal-oral route, which can occur from direct person-to-person contact, from contamination of the environment or objects, or through contaminated food or water. (1)
Mechanism of Action
AVAXIM® - Pediatric confers immunity against HAV infection by inducing the production of specific anti-HAV antibodies.
Pharmacodynamics
In clinical studies involving over 1,000 adult volunteers, specific humoral antibodies against hepatitis A were elicited after the first injection and more than 95% of immunocompetent subjects were protected (titres above 20 mIU/mL) 14 days after vaccination. One month after the first injection, 100% of the subjects were protected. (6)
In clinical studies for immunogenicity in 656 children aged 12 months to 15 years (inclusive), seroconversion rates 2 weeks following vaccination ranged from 95.4% to 99.1% depending on the study. One hundred percent of those tested at 24 and 28 weeks following vaccination had protective antibody levels. (6) (13) (14)
Duration of Effect
A descriptive, prospective, mono-centre, antibody persistence study conducted in 546 Argentinean children provided long-term antibody persistence data on two groups; one group who received a single dose of AVAXIM® - Pediatric and another group who received the standard two-dose schedule. It was shown 7 years after vaccination that the group who received a single dose of AVAXIM® - Pediatric (N=204) had a similar seroprotective level of anti-HAV antibodies as the group who received two doses (N=53). (15) (16)
Data relative to long-term persistence of anti-HAV antibodies following booster vaccination with AVAXIM® - Pediatric indicate that anti-HAV antibodies persist up to 14-15 years in healthy individuals. (17) According to NACI, protective levels of anti-HAV antibody will likely persist for at least 20 years, possibly for life, following immunization with two doses of hepatitis A-containing vaccine. (1)
STORAGE AND STABILITY
Store at 2° to 8°C (35° to 46°F). Do not freeze. Discard product if exposed to freezing. Do not use vaccine after expiration date.
DOSAGE FORMS, COMPOSITION AND PACKAGING
Dosage Forms
AVAXIM® - Pediatric is supplied as a sterile, whitish, cloudy suspension.
Composition
Each dose (0.5 mL) is formulated to contain:
Active Ingredient
Inactivated Hepatitis A Virus, GBM strain 80 antigen units†
Other Ingredients
Excipients
2-phenoxyethanol 2.5 µL
Formaldehyde 12.5 µg
Aluminum hydroxide (expressed as aluminum) 0.15 mg
Medium 199 Hanks‡ in water for injection up to 0.5 mL
Polysorbate 80‡ ≤750 µg
Manufacturing Process Residuals
Neomycin is present in trace amounts.
† In the absence of an international standardized reference, the antigen content is expressed using an in-house reference.
‡ Medium 199 Hanks (without phenol red) is a mixture of amino acids, mineral salts, vitamins and other components supplemented with polysorbate 80.
Packaging
The plunger stoppers and needle shield for the syringes and the vial stoppers do not contain latex (natural rubber).
AVAXIM® - Pediatric is supplied in packages of:
1 x 0.5 mL (single dose) syringe with attached needle.
1 x 0.5 mL (single dose) syringe with choice of two needles (1 x 25G x 16 mm and 1 x 25G x 25 mm).
1 x 10 dose vial.
Vaccine Information Service: 1-888-621-1146 or 416-667-2779.
Full product monograph available on request or visit us at www.sanofi.ca
Product information as of March 2019.
Fabricated by:
Sanofi Pasteur SA
Lyon, France
Manufactured and distributed by:
Sanofi Pasteur Limited
Toronto, Ontario, Canada
R6-0319 Canada
PART II: SCIENTIFIC INFORMATION
PHARMACEUTICAL INFORMATION
Drug Substance
Proper name: Hepatitis A Vaccine Inactivated
Product Characteristics
AVAXIM® - Pediatric [Hepatitis A Vaccine Inactivated] is a sterile, cloudy, whitish suspension of inactivated hepatitis A.
The active ingredient is a purified and formaldehyde-inactivated hepatitis A virus (HAV) obtained from the GBM strain cultured on MRC-5 human diploid cells. HAV is adsorbed onto aluminum. Each dose (0.5 mL) of inactivated hepatitis A vaccine contains 80 antigen units (in the absence of an international standardized reference, the antigen content is expressed using an in-house reference).
CLINICAL TRIALS
Table 2: Summary of Demographics and Study Design of the Pivotal Trials with AVAXIM® - Pediatric (6) (12) (15)
| Study # | Trial Design | Dosage, Route of Administration and Duration | Study Subjects | Age Range | Gender |
|---|---|---|---|---|---|
| HAF11395 | Unicentre, open, non-controlled study with three age groups and direct individual benefit | 0.5 mL I.M. 1 Dose + Booster | N = 189 | 18 months – 15 years 18 months – 4 years (N = 42) 4 – 9 years (N = 59) 9 – 15 years (N = 88) | Males N = 103 Females N = 86 |
| HAF17396 | Multicentre, open, non-controlled, descriptive with direct individual benefit. | 0.5 mL I.M. 1 Dose + Booster | N = 1244 | 18 months – 15 years 18 months – 4 | Males N = 652 Females |
| Study # | Trial Design | Dosage, Route of Administration and Duration | Study Subjects | Age Range | Gender |
|---|---|---|---|---|---|
years (N = 353) 4 – 9 years (N = 463) 9 – 15 years (N = 428) | N = 592 | ||||
| HAF19396 | Multicentre, open, non-controlled, with direct individual benefit. | 0.5 mL I.M. 1 Dose + Booster | N = 597 | 18 months – 15 years 18 months – 4 years (N = 200) 4 – 9 years (N = 197) 9 – 15 years (N = 200) | Males N = 301 Females N = 296 |
| HAF20396 | Unicentre, open, non-controlled, with direct individual benefit. | 0.5 mL I.M. 1 Dose + Booster | N = 537 | 12 months – 15 years 12 months – 4 years (N = 257) 4 – 9 years (N = 163) 9 – 15 years (N = 117) | Males N = 292 Females N = 245 |
| HAF82 | Unicentre descriptive prospective cohort study (epidemiological trial). | Not applicable | N = 546 | 24 – 39 months | Males N = 271 Females N = 275 |
| HAF65 | Multi-center, randomized, blind observer, controlled study. | 0.5 mL I.M. 1 Dose + Booster (concomitant or separately 1 dose MMR) | N = 470 | 12 – 13 months | Males N = 261 Females N = 209 |
Immunogenicity
Clinical studies indicate that the vaccine confers immunity against HAV by inducing antibody titres greater than those obtained after passive immunization with immunoglobulin. Immunity appears shortly after the first injection. (6) (18)
In clinical studies for immunogenicity in 656 children aged 12 months to 15 years (inclusive), seroconversion rates 2 weeks following vaccination ranged from 95.4% to 99.1% depending on the study. One hundred percent of those tested at 24 and 28 weeks following vaccination had protective antibody levels. (6) (13) (14) A second dose given 6 months following the initial dose resulted in a marked booster response (increase in antibody titres of 22.6-fold and 35.5-fold).
In clinical studies involving over 1,000 adult volunteers, specific humoral antibodies against hepatitis A were elicited after the first injection and more than 90% of immunocompetent subjects were protected (titres above 20 mIU/mL) 14 days after vaccination. One month after the first injection, 100% of the subjects were protected. Immunity persisted for at least 36 months and was reinforced after a booster dose. (19) (15)
In comparative trials with another hepatitis A vaccine, AVAXIM® - Pediatric demonstrated a superior immunogenicity profile. (4) (20) Although seroconversion rates at 14 days were similar to that of the other hepatitis A vaccine, GMTs were significantly higher following AVAXIM® - Pediatric. (21) (22) This prompt immune response may be an important consideration when travellers must be vaccinated immediately prior to departure or when post-exposure prophylaxis cannot be done immediately after exposure. (1)
A descriptive, prospective, mono-centre, antibody persistence study was conducted in a cohort of 546 Argentinean subjects who received 1 or 2 doses of AVAXIM® - Pediatric before inclusion and were 11 to 23 months old at the time of the first vaccine dose administration. The subjects were followed-up on a yearly basis and blood samples were collected to determine the concentration of anti-HAV antibody up to 7 years after hepatitis A vaccination course. This study showed that the seroprotection rate remained high 3, 5 and 7 years after hepatitis A vaccination course, including in subjects who received only a single dose of AVAXIM® - Pediatric. At Year 7, the seroprotection rate (defined as the proportion of subjects with anti-HAV IgG concentrations ≥3 mIU/mL, using electrochemiluminescence immunoassay) was 100.0% in subjects who received 1 dose (N=204) or 2 doses (N=53) of AVAXIM® - Pediatric. Anti-HAV IgG titers were well above the seroprotective thresholds up to 7 years after hepatitis A vaccination course, including in subjects who received only a single dose of AVAXIM® - Pediatric, but tended to decrease all along the 7 years after vaccination. (15) (16)
A randomized, blind-observer, controlled trial was conducted in Turkey to compare the immunogenicity of AVAXIM®-Pediatric administered alone or concomitantly but at different sites with Sanofi Pasteur's MMR vaccine, in HAV seronegative children, 12 to 13 months of age. A total of 470 subjects were randomly assigned to one of three groups and received a dose of either AVAXIM® -Pediatric or MMR vaccine alone, or both vaccines concomitantly (at separate sites) on D0. All groups received one booster dose of AVAXIM® - Pediatric vaccine on Day 213.
| D0 | D28 | Booster D213 | |||||||||||
| Group | AVAXIM® - Pediatric | MMR | AVAXIM® - Pediatric | MMR | AVAXIM® - Pediatric | ||||||||
| A | X | X | X | ||||||||||
| B | X | X | X | ||||||||||
| C | X | X | X | ||||||||||
The primary parameter was the difference in seroprotection rates (anti-HAV antibody titer ≥20 mIU/mL on D28) between the Group C and Group A. Non-inferiority was defined as the lower limit of the 95% CI of this difference being ≥-5%. (12) As shown in Table 3, when AVAXIM® - Pediatric was administered alone or concomitantly with Sanofi Pasteur’s MMR vaccine, high anti-HAV antibody titers were induced and seroprotection was achieved in 92.7% to 93.6% of subjects. (12)
Table 3: Anti-HAV Seroprotection Rates on Day 28
Group A N=172 | Group C N=164 | Group C - Group A | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n | % | n | % | Difference with 95% CI | |||||||||
| Anti-HAV ≥20 mIU/mL | 161 | 93.60 | 152 | 92.68 | -0.92 [-6.68;4.69] | ||||||||
Previous concomitant AVAXIM® - Pediatric and MMR did not impact the anamnestic response to a booster dose of AVAXIM® - Pediatric. (12)
Safety
A pooled analysis of safety data from 5,458 subjects who received AVAXIM® - Pediatric in 15 clinical trials was performed. (See ADVERSE REACTIONS, PART I.)
In clinical trials conducted with AVAXIM® - Pediatric, adverse events were usually mild and confined to the first few days after vaccination with spontaneous recovery. (6) (13) (14) Younger children experienced fewer reactions than older children. Reactions were reported less frequently after the booster dose than after the first dose.
Mild transient elevation of serum transaminases has been reported on rare occasions. (6) (14)
In subjects seropositive to HAV, AVAXIM® - Pediatric was as well tolerated as in seronegative subjects.
The safety results of clinical trial HAF65 studying concomitant administration of AVAXIM® - Pediatric and Sanofi Pasteur’s MMR vaccine were consistent with the safety profile of each individual vaccine and showed a tendency towards a greater number of subjects experiencing at least one systemic reaction when AVAXIM® - Pediatric and Sanofi Pasteur’s MMR vaccine were administered concomitantly. (12)
Vaccine Information Service: 1-888-621-1146 or 416-667-2779.
Full product monograph available on request or visit us at www.sanofi.ca
Product information as of March 2019.
Fabricated by:
Sanofi Pasteur SA
Lyon, France
Manufactured and distributed by: Sanofi Pasteur Limited Toronto, Ontario, Canada
R6-0319 Canada
REFERENCES
1 Public Health Agency of Canada (PHAC). Part 4 - Active Vaccines: Hepatitis A Vaccine. In: Canadian Immunization Guide. [Online]. 2018. Available from: URL: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-6-hepatitis-a-vaccine.html
2 Zuckerman J, et al. Immunogenicity and reactogenicity of AVAXIM® (160 AU) as compared with Havrix (1440 EL.U.) as a booster following primary immunization with Havrix (1400 EL.U.) against Hepatitis A. J of Travel Medicine 1998;5(1):18-22.
3 Clarke P, et al. A randomised comparison of two inactivated hepatitis A vaccines, Avaxim and Vaqta, given as a booster to subjects primed with Avaxim. Vaccine 2001;19(31):4429-33.
4 Zuckerman J, et al. Comparison of the safety and immunogenicity of two inactivated hepatitis A vaccines. Adv Therapy 1997;14(3):116-24.
5 CDC. General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006;55(RR-15):1-48.
6 Data on file at Sanofi Pasteur Limited.
7 Fisch A, et al. Immunogenicity and safety of a new inactivated hepatitis A vaccine: a clinical trial with comparison of administration route. Vaccine 1996;14(12):1132-6.
8 Public Health Agency of Canada (PHAC). Part 2 - Vaccine Safety: Early vaccine reactions including anaphylaxis. In: Canadian Immunization Guide. [Online]. 2013. Available from: URL: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-2-vaccine-safety/page-4-early-vaccine-reactions-including-anaphylaxis.html
9 Public Health Agency of Canada (PHAC). Part 3 - Vaccination of Specific Populations: Immunization of immunocompromised persons. In: Canadian Immunization Guide. [Online]. 2018. Available from: URL: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-3-vaccination-specific-populations/page-8-immunization-immunocompromised-persons.html
10 Zanetti A, et al. Does immunoglobulin interfere with the immunogenicity to Pasteur Merieux inactivated hepatitis A vaccine? J Hepatol 1997;26:25-30.
11 Yurdakök K, et al. Immunogenicity and Safety of an Inactivated Hepatitis A Vaccine Given with Measles-Mumps-Rubella Vaccine to 12-13 Month Old Turkish Children. J Vaccines Vaccin 2012;3:1-7.
12 Data on file at Sanofi Pasteur Limited. Clinical Study Report HAF65.
13 Dagan R, et al. Safety and immunogenicity of a new formulation of an inactivated hepatitis A vaccine. Vaccine 1999;17:1919-25.
14 Castillo de Febres O, et al. Safety, immunogenicity and antibody persistence of an inactivated hepatitis A vaccine in 4 to 15 year old children. Vaccine 2000;18:656-64.
15 Data on file at Sanofi Pasteur Limited. Clinical Study Report HAF82.
16 Espul C, Benedetti L, Linares M, Cuello H, Castro IL, Thollot Y, Rasuli A; Seven-year follow-up of the immune response after one or two doses of inactivated hepatitis A vaccine given at 1 year of age in the Mendoza Province of Argentina, Hum Vaccin Immunother. 2017 Sep 21:0.
17 López E.L., Contrini M.M., Mistchenko A., Kieffer A., Baggaley R.F., Di Tanna G.L., Desai K., Rasuli A., Armoni J. Modeling the long-term persistence of hepatitis a antibody after a two-dose vaccination schedule in Argentinean children. Pediatric Infectious Disease Journal 2015 34:4 (417-25).
18 Vidor E, et al. Aventis Pasteur vaccines containing inactivated hepatitis A virus: a compilation of immunogenicity data. Eur J Clin Microbiol Infect Dis. 2004; 23(4):300-9.
19 Espul C, et al. Persistence of immunity from 1 year of age after one or two doses of hepatitis A vaccine given to children in Argentina. Hepatic Medicine: Evidence and Research 2012;4:53-60.
20 Flehming B, et al. Early appearance of neutralizing antibodies after vaccination with an inactivated hepatitis A vaccine. J Infect 1997;35:37-40.
21 Abarca K. Immunogenicity, safety, and interchangeability of two inactivated hepatitis A vaccines in Chilean children. Int J Infect Dis. 2008; 270-7.
22 Soysal A. Interchangeability of a hepatitis A vaccine second dose: Avaxim 80 following a first dose of Vaqta 25 or Havrix 720 in children in Turkey. J Pediatr. 2007; 533-9.