Product Monograph - Avaxim
RECENT MAJOR LABEL CHANGES
| 1 Indications | 2023-04 |
|---|---|
| 4 Dosage and Administration | 2023-04 |
| Patient Medication Information | /2023-04 |
| 2025-03 |
| Patient Medication Information | 2025-03 |
TABLE OF CONTENTS
Sections or subsections that are not applicable at the time of authorization are not listed.
RECENT MAJOR LABEL CHANGES .......................................................................................... 2
PART I: Healthcare Professional Information ......................................................................... 4
1 Indications ................................................................................................................ 4
1.1 Pediatrics ................................................................................................................ 4
1.2 Geriatrics ................................................................................................................ 4
2 Contraindications ...................................................................................................... 4
4 Dosage and Administration ....................................................................................... 4
4.1 Dosing Considerations ........................................................................................... 4
4.2 Recommended Dose and Dosage Adjustment ...................................................... 4
4.4 Administration ....................................................................................................... 5
5 Overdosage ............................................................................................................... 5
6 Dosage Forms, Strengths, Composition and Packaging ............................................... 5
7 Warnings and Precautions ......................................................................................... 7
General ............................................................................................................................... 7
Febrile or Acute Disease .................................................................................................... 7
Hematologic ....................................................................................................................... 8
Immune .............................................................................................................................. 8
Protection .......................................................................................................................... 8
7.1 Special Populations ................................................................................................ 8
7.1.1 Pregnant Women ............................................................................................... 8
7.1.2 Breast-feeding .................................................................................................... 9
7.1.4 Geriatrics ............................................................................................................ 9
8 Adverse Reactions ..................................................................................................... 9
8.1 Adverse Reaction Overview ................................................................................... 9
8.2 Clinical Trial Adverse Reactions ............................................................................. 9
8.5 Post-Market Adverse Reactions ........................................................................... 10
9 Drug Interactions .................................................................................................... 11
9.4 Drug-Drug Interactions ........................................................................................ 11
10 Clinical Pharmacology ............................................................................................. 11
10.1 Mechanism of Action ........................................................................................... 11
10.2 Pharmacodynamics .............................................................................................. 12
10.3 Pharmacokinetics ................................................................................................. 12
11 STORAGE, STABILITY AND DISPOSAL ........................................................................ 12
12 SPECIAL HANDLING INSTRUCTIONS .......................................................................... 12
PART II: Scientific Information ............................................................................................ 13
13 Pharmaceutical Information .................................................................................... 13
14 Clinical Trials ........................................................................................................... 13
14.1 Trial Design and Study Demographics ................................................................. 13
14.4 Immunogenicity ................................................................................................... 14
15 Microbiology ........................................................................................................... 14
16 Non-Clinical Toxicology ........................................................................................... 14
Patient Medication Information ......................................................................................... 15
PART I: Healthcare Professional Information
1 Indications
AVAXIM® is indicated for active immunization against infection caused by hepatitis A virus (HAV) in persons 12 years of age and older. AVAXIM® can be used for primary immunization or as a booster following primary immunization with AVAXIM® or other similar hepatitis A vaccines.
1.1 Pediatrics
AVAXIM® is not indicated for immunization of persons below the age of 12 years. AVAXIM® may be used for persons between 12 through 18 years of age.
1.2 Geriatrics
Geriatrics: Limited data are available to Health Canada. (see Warnings and Precautions and
CLINICAL TRIALS).
2 Contraindications
AVAXIM® is contraindicated in patients who are hypersensitive to this vaccine after previous administration or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing 6 Dosage Forms, Strengths, Composition and Packaging .
4 Dosage and Administration
4.1 Dosing Considerations
Administration Route Related Precautions:
Do not administer AVAXIM® by intravascular injection: ensure that the needle does not penetrate a blood vessel.
Do not administer intradermally.
AVAXIM® should not be administered into the buttocks.
- For more information, refer to the National Advisory Committee on Immunization and the Canadian Immunization Guide for current recommendations on the use of vaccines in Canada.
4.2 Recommended Dose and Dosage Adjustment
AVAXIM® should be administered as a single injection of 1 dose (0.5 mL) by the intramuscular route.
Primary immunization consists of one dose of vaccine, followed by a booster dose 6 to 36 months later in order to confer long term protection.
4.4 Administration
Inspect for extraneous particulate matter and/or discolouration before use. If these conditions exist, the product should not be administered.
Shake the pre-filled syringe well until a uniform, cloudy suspension results.
AVAXIM® may be packaged in one of two presentations: a pre-filled syringe with a needle, or a pre-filled syringe with attached needle.
If a syringe does not have an attached need, remove the tip cap from the syringe, take the 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.
Aseptic technique must be used. Use a separate sterile needle and syringe, or a sterile disposable unit for each individual patient to prevent disease transmission. 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.
5 Overdosage
For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764-7669)
6 Dosage Forms, Strengths, Composition and Packaging
To help ensure the traceability of vaccines for patient immunization record-keeping as well as safety monitoring, health professionals should record the time and date of administration, quantity of administered dose (if applicable), anatomical site and route of administration, brand name and generic name of the vaccine, the product lot number and expiry date.
Table 1: Dosage Forms, Strengths, and Composition
Description
AVAXIM® is supplied as a sterile, whitish, cloudy suspension in a pre-filled syringe.
Each dose (0.5 mL) is formulated to contain: 160 EU (ELISA Unit) of Hepatitis A Virus, GBM strain (inactivated). In the absence of an international standardized reference, the antigen content is expressed in EU using an in-house reference.
The non-medicinal ingredients are as follows: Phenoxyethanol-Ethanol (50% v/v solution) with
2 phenoxyethanol (2.5 µL) and ethanol anhydrous (2.5 µL); Formaldehyde (12.5 mcg); Aluminum hydroxide, hydrated (expressed as aluminum 0.3 mg); 1 x C Medium 199 Hanks (up to 0.5 mL).
1 x C Medium 199 Hanks (without phenol red) is a complex mixture of amino acids (including phenylalanine), mineral salts, vitamins and other components supplemented with polysorbate 80 and is reconstituted in water for injection. Hydrochloric acid and or sodium hydroxide can be used for pH adjustment; these components are only present in trace amounts. Neomycin is also present in trace amounts.
Packaging:
AVAXIM® is supplied in pre-filled single dose syringes.
The syringes are made of Type 1 glass. The plunger stoppers and needle shield for the syringes do not contain latex (natural rubber).
AVAXIM® is supplied in packages of:
1 x 0.5 mL (single dose) syringe with one needle (1 x 25G x 25 mm).
| Route of Administration | Dosage Form / Strength/Composition | Non-medicinal Ingredients |
| Intramuscular injection | Suspension for injection Each 0.5 mL dose is formulated to contain: Active Ingredient: Hepatitis A Virus Inactivated (GBM strain): 160 antigen units (U) | 2-phenoxyethanol, aluminum hydroxide (expressed as aluminum), ethanol anhydrous, formaldehyde, Medium 199 Hanks, Manufacturing process residuals: neomycin |
7 Warnings and Precautions
General
Before administration of AVAXIM®, 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® will prevent hepatitis A in this case.
Seropositivity against HAV is not a contraindication.
As with any vaccine, AVAXIM® may not protect 100% of vaccinated individuals.
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.
As each dose may contain traces of formaldehyde, caution should be exercised when the vaccine is administered to subjects with hypersensitivity to this product.
As each dose may contain undetectable traces of neomycin, which is used during vaccine production, caution should be exercised when the vaccine is administered to subjects with hypersensitivity to this antibiotic (and other antibiotics of the same class).
No studies have been performed with Avaxim in subjects with liver disease. The use of this vaccine in such subjects should be considered with care.
Febrile or Acute Disease
Vaccination should be postponed in cases of an acute or febrile disease. However, a disease with a low-grade fever should not usually be a reason to postpone vaccination.
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® 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.
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® even in persons with no prior history of hypersensitivity to the product components (See 6 Dosage Forms, Strengths, 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. Health-care providers should be familiar with current recommendations for the initial management of anaphylaxis in non-hospital settings, including proper airway management.
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. Nevertheless, vaccination of persons with chronic immunodeficiency such as HIV infection is recommended even if the antibody response might be limited.
Protection
AVAXIM® does not provide protection against infection caused by hepatitis B virus, hepatitis C virus, delta virus, hepatitis E virus, or by other liver pathogens, other than hepatitis A virus.
7.1 Special Populations
7.1.1 Pregnancy
Animal reproduction studies have not been conducted with AVAXIM®.
Data on the use of this vaccine in pregnant woman are limited. Therefore, the administration of the vaccine during pregnancy is not recommended. AVAXIM® should be given to pregnant women only if clearly needed and following an assessment of its risks and benefits.
7.1.2 Breast-feeding
It is not known whether this vaccine is excreted in human milk. Caution must be exercised when AVAXIM® is administered to a nursing mother.
7.1.4 Geriatrics
Clinical studies of AVAXIM did not include subjects aged 65 years and older to determine whether they respond differently from younger subjects. Clinical experience from Hepatitis A vaccines has not identified differences in overall safety between these subjects and younger adult subjects.
8 Adverse Reactions
8.1 Adverse Reaction Overview
The most commonly reported adverse reactions were asthenia (13.5%), injection site pain occasionally associated with redness (0.5% over 3 cm) (11.7%), muscle or joint ache (10.3%) and headache (9.7%). %). Mild fever (5.2%) and gastrointestinal tract disorders (6.1%) such as nausea, vomiting, diarrhea, or pain, were also reported.
8.2 Clinical Trial Adverse Reactions
Because clinical trials are conducted under widely varying 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.
In six clinical trials conducted which involved over 2,200 participants, adverse events were usually mild and confined to the first few days after vaccination with spontaneous recovery.
Table 2: Frequency (%) of Reactions Observed After One Dose of AVAXIM®
| Reaction | % of Persons with a Reaction (N = 2,204) |
| Reaction | % of Persons with a Reaction (N = 2,204) |
| Local Reactions | |
| Pain | 11.7 |
| Redness | 0.5 |
| Systemic Reactions | |
| Asthenia (weakness) | 13.5 |
| Myalgia/Arthralgia (muscle or joint ache) | 10.3 |
| Headache | 9.7 |
| Gastrointestinal Tract Disorders (nausea, vomiting, diarrhea, pain) | 6.1 |
| Mild Fever (≥38.0°C to ≤38.4°C) | 5.2 |
Mild transient elevation of serum transaminases has been reported on rare occasions. The appearance of a nodule at the injection site was observed in very rare cases.
Adverse reactions were less frequently reported after the booster dose than after the first dose.
In subjects seropositive to HAV, AVAXIM® was as well tolerated as in seronegative subjects. The reactions observed in haemophiliac children were identical to those observed in adults.
In comparative trials with another hepatitis A vaccine, in a total of 423 adults, AVAXIM® demonstrated significantly fewer local reactions after each injection.
8.5 Post-Market Adverse Reactions
The following additional adverse reactions have been spontaneously reported during the post-marketing use of AVAXIM®. 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 event, 2) frequency of reporting, or 3) strength of causal connection to AVAXIM®.
Blood and Lymphatic system disorder
- Lymphadenopathy
Immune system disorders
- Anaphylactic reaction
Nervous system disorders
- Vasovagal syncope, headache
Gastrointestinal disorders
Nausea, diarrhea, vomiting, abdominal pain
Skin and subcutaneous tissue disorders
Urticaria, rashes with or without pruritus
Musculoskeletal and connective tissue disorders
Arthralgia, myalgia
General disorders and administration site condition
Injection site pain, injection site rash, injection site nodule, pyrexia, asthenia
Investigations
Transaminases increased (mild and reversible)
Physicians, nurses and pharmacists should report any adverse reaction temporally related to the administration of the product in accordance with local requirements (See Patient Medication Information , Reporting Side Effects for Vaccines).
9 Drug Interactions
9.4 Drug-Drug Interactions
Vaccine-Drug Interactions:
Immunosuppressive treatments may interfere with the development of the expected immune response. (See 7 Warnings and Precautions).
Separate injection sites and separate syringes must be used in case of concomitant administration with other medicinal products.
Concomitant Vaccine Administration:
AVAXIM® 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.
As the vaccine is inactivated, concomitant administration of other vaccine(s) given at other injection sites is unlikely to interfere with immune responses. No interaction with other medication is currently known. AVAXIM® has been shown to be safe and immunogenic when concomitantly administered with TYPHIM Vi® and live yellow fever vaccine using separate syringes at different sites.
Vaccines administered simultaneously must be given using separate syringes at separate sites.
10 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.
10.1 Mechanism of Action
AVAXIM® confers immunity against HAV infection by inducing the production of specific anti-HAV antibodies.
10.2 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 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.
In a clinical trial, an assessment of the persistence of HAV antibodies showed more than 99% (n = 103) of subjects were still protected (titre ≥20 mIU/mL) 3 years after the initial dose of AVAXIM®.
10.3 Pharmacokinetics
Duration of Effect
Data relative to long-term persistence of anti-HAV antibodies following vaccination with AVAXIM® are not currently available. Published data suggest that anti-HAV antibodies persist beyond 10 years after the booster vaccination in healthy individuals. According to NACI, kinetic models of antibody decline suggest that protective levels of anti-HAV antibody will likely persist for at least 20 years.
11 Storage, Stability and Disposal
Store at 2° to 8°C (35° to 46°F). Do not freeze. Discard product if exposed to freezing. Protect from light.
12 Special Handling Instructions
Do not use the vaccine after the expiration date.
Part II: Scientific Information
13 Pharmaceutical Information
Drug Substance
Proper name: Hepatitis A virus Inactivated
Product Characteristics:
AVAXIM® [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 160 antigen units (in the absence of an international standardized reference, the antigen content is expressed using an in-house reference).
14 Clinical Trials
14.1 Trial Design and Study Demographics
Table 3: Summary of Demographics and Study Design of the Trials with AVAXIM®
| Study # | Trial Design | Dosage, Route of Administration and Duration | Study Subjects | Age Range | Gender |
| Study # | Trial Design | Dosage, Route of Administration and Duration | Study Subjects | Age Range | Gender |
| HAF03293 | Randomized, open, multicentre, controlled, comparative study on administration routes. | 0.5 mL I.M., S.C., Jet Injector 1 Dose + Booster | N = 147 | 19 – 60 Years | Males N = 58 Females N = 89 |
| HAF05392 | Randomized, open, multicentre, controlled, comparative study between AVAXIM® and another HAV vaccine. | AVAXIM® 0.5 mL I.M. HAV vaccine 1 mL I.M. 1 Dose + Booster | N = 840 | 18 – 60 Years | Males N = 275 Females N = 565 |
| HAF06393 | Randomized, double-blinded, /multicentre, descriptive study for HAV antibody titres and immunogenicity. | 0.5 mL I.M. 1 Dose + Booster | N = 243 | 16 – 60 Years | Males N = 213 Females N = 30 |
| HAF07393 | Monocentre, open, controlled, comparative | 0.5 mL I.M. | N = 80 | 18 – 60 Years | Males N = 50 |
| study on immunogenicity | 1 Dose + Booster | Females N = 30 | |||
| HAF08393 | Multicentre, open, non-controlled trial descriptive study on local and systemic reactions. | 0.5 mL I.M. 1 Dose + Booster | N = 2159 | 18 – 60 Years | Males N = 2065 Females N = 94 |
| AVi01398 | Multicentre, open, randomized comparison study between HA/Vi vaccine and concomitant administration of hepatitis A and typhoid fever vaccines | 1 Dose, 1.0 mL I.M. of HA/Vi Vaccine or 1 Dose, 0.5 mL I.M. each of Hepatitis A and Typhoid Fever Vaccine | N = 360 | 16 – 65 Years | Males N = 144 Females N = 216 |
14.4 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.
In clinical studies involving over 1,000 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.
In comparative trials with another hepatitis A vaccine, AVAXIM® demonstrated a superior immunogenicity profile. Additionally, seroconversion rates at 14 days showed that the immune responses occur more rapidly with AVAXIM®. 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.
15 Microbiology
No microbiological information is required for this drug product.
16 Non-Clinical Toxicology
Available data in animals revealed no unexpected findings and no target organ toxicity.