Consumer medicine information

IMOJEV

Japanese encephalitis vaccine (live, attenuated, recombinant)

BRAND INFORMATION

Brand name

Imojev

Active ingredient

Japanese encephalitis vaccine (live, attenuated, recombinant)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using IMOJEV.

SUMMARY CMI

Imojev®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Imojev?

Imojev contains the active ingredient Japanese encephalitis virus (live, attenuated). Imojev is used to help to protect you or your child against Japanese encephalitis.

For more information, see Section 1. Why am I using Imojev? in the full CMI.

2. What should I know before I use Imojev?

Do not use if you have ever had an allergic reaction to Imojev or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Imojev? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Imojev and affect how it works. Tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other vaccines or medicines, including medicines obtained without a prescription.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Imojev?

Imojev is given by your doctor, nurse or pharmacist.

More instructions can be found in Section 4. How do I use Imojev? in the full CMI.

5. What should I know while using Imojev?

Things you should doTell your doctor, nurse or pharmacist before you receive the vaccine:
  • If you or your child is allergic to the active ingredients, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you or your child can use this medicine.
  • If you or your child has an illness with febrile or acute disease. The vaccination should be postponed until after you or your child has recovered,
  • If you or your child has lowered immunity due to treatment with medicines such as corticosteroids or other medicines used to treat cancer (chemotherapy) (see Taking other medicines section),
  • If you or your child has lowered immunity due to diseases including HIV / AIDS or cancer,
  • If you are pregnant or breast-feeding,
  • If you think you may be pregnant, or if you intend to become pregnant within four weeks of vaccination,
  • If you or your child has had a blood or plasma transfusion or received injection of immunoglobulins (blood products used to prevent some infections) in the last 3 months. Your doctor may decide to delay vaccination.
Looking after your medicine
  • Imojev is usually stored in the surgery or clinic, or at the pharmacy. However, if you need to store Imojev, keep in the fridge between 2-8°C. Do not freeze.

For more information, see Section 5. What should I know while using Imojev? in the full CMI.

6. Are there any side effects?

Most common side effects in adults include tiredness, feeling unwell, injection site pain, headache, muscular pain, feeling hot, chills, injection site redness, injection site itching, injection site swelling, injection site bruising, dizziness, joint pain, diarrhoea, nausea, abdominal pain, vomiting, throat pain, shortness of breath, runny nose, cough, wheezing, nasal congestion and rash. In children, most common side effects include fever, feeling unwell, irritability, injection site pain, injection site redness, headache, sleepiness, muscular pain, vomiting, loss of appetite, inconsolable crying and injection site swelling.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Imojev®

Active ingredient(s): Japanese encephalitis virus (live, attenuated)


Consumer Medicine Information (CMI)

This leaflet provides important information about using Imojev. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Imojev.

Where to find information in this leaflet:

1. Why am I using Imojev?
2. What should I know before I use Imojev?
3. What if I am taking other medicines?
4. How do I use Imojev?
5. What should I know while using Imojev?
6. Are there any side effects?
7. Product details

1. Why am I using Imojev?

Imojev contains the active ingredient Japanese encephalitis virus (live, attenuated).

Imojev is a vaccine for persons of 9 months of age and over that helps to protect you or your child against Japanese encephalitis.

When an injection of Imojev is given, the immune system (body's natural defences) will protect against Japanese encephalitis infection. However, as with all vaccines, 100% protection cannot be guaranteed.

In adults, Imojev will generally begin protecting against Japanese encephalitis 2 weeks after the injection.

In children, Imojev will generally begin protecting against Japanese encephalitis 4 weeks after the injection.

Imojev will not prevent Japanese encephalitis if you or your child is incubating the disease before vaccination or if the encephalitis is caused by another virus.

2. What should I know before I use Imojev?

Warnings

Do not use Imojev:

  • If you or your child is allergic to the active ingredients, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you or your child can receive this vaccine.
  • If you or your child has an illness with febrile or acute disease. The vaccination should be postponed until after you or your child has recovered,
  • If you or your child has lowered immunity due to treatment with medicines such as corticosteroids or other medicines used to treat cancer (chemotherapy) (see Taking other medicines section),
  • If you or your child has lowered immunity due to diseases including HIV / AIDS or cancer,
  • If you are pregnant,
  • If you think you may be pregnant, or if you intend to become pregnant within four weeks of vaccination,
  • If you are breast-feeding.

Check with your doctor if you or your child:

  • has had a blood or plasma transfusion or received injection of immunoglobulins (blood products used to prevent some infections) in the last 3 months. Your doctor may decide to delay vaccination.
  • takes any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Imojev must not be used during pregnancy.

If you are planning to become pregnant, you must wait four weeks after vaccination before trying to conceive.

Imojev must not be used during breast-feeding.

3. What if I am taking other medicines?

Some medicines may interfere with Imojev and affect how it works.

If you or your child is taking medicines that may reduce your immune response such as corticosteroids (for example prednisone), medicines used to treat cancer (chemotherapy), radiotherapy or other medicines affecting the immune system, be sure to tell your doctor.

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Your doctor will advise you if Imojev can be given with another vaccine.

In adults, Imojev may be given at the same time as the yellow fever vaccine using separate syringes, and injected into separate limbs. In children, Imojev may be given at the same time as vaccines against measles, mumps and rubella using separate syringes, and injected into separate limbs from 12 months of age. For children living in or travelling to areas where risk for measles is high, Imojev may be given at the same time as vaccines against measles, mumps and rubella from as early as 9 months of age.

Tell your doctor if you or your child has had any vaccine in the last 4 weeks.

Tell your doctor that your or your child has received Imojev if another vaccine is to be given within 4 weeks after vaccination.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Imojev.

4. How do I use Imojev?

How much to use

Imojev is administered to you or your child by your doctor or your nurse as a 0.5 mL injection under the skin in the upper arm. For toddlers (9 to 24 months), Imojev can also be given in the upper thigh area.

  • For persons from 9 months to 17 years of age, if long-term protection is required, a booster dose should be given preferably 1 year after the first vaccination. The booster dose can be given up to 2 years after the first vaccination.
  • For persons aged 18 years and over there is no need for a booster dose up to 5 years after the first vaccination.
  • Imojev should not be injected directly into veins.
  • Contact with disinfectants is to be avoided since they may destroy the vaccine.

If you use too much Imojev

If you think that you have used too much Imojev, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Imojev?

Things you should do

Call your doctor straight away if you:

  • You notice signs of allergic reaction may include difficulty breathing, shortness of breath, swelling of the face, lips, throat or tongue, cold, clammy skin, palpitations, dizziness, weakness, fainting, rash or itching.

Remind any doctor or dentist you visit that you are using Imojev.

Driving or using machines

Imojev has no or negligible effect on your ability to drive and use machine.

Looking after your medicine

Imojev is usually stored in the doctor's surgery or clinic, or at the pharmacy. However, if you need to store Imojev:

  • Keep it where young children cannot reach it.
  • Keep Imojev in the original pack until it is time for it to be given.
  • Keep it in the refrigerator, store at 2°C to 8°C. Do not freeze Imojev.
  • Do not use Imojev after the expiry date which is stated on the carton after EXP.
  • Do not use Imojev if the packaging is torn or shows signs of tampering.

Getting rid of any unwanted medicine

Medicines including vaccines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Adults
  • Tiredness (fatigue), feeling unwell (malaise), injection site pain
  • Headache
  • Muscular pain (myalgia)
  • Feeling hot, chills, injection site redness (erythema), injection site itching (pruritus), injection site swelling, injection site bruising,
  • Dizziness,
  • Joint pain (arthralgia),
  • Diarrhoea, nausea, abdominal pain, vomiting,
  • Rash,
  • Fever (pyrexia).
Children
  • Fever (pyrexia), feeling unwell (malaise), irritability, injection site pain/tenderness, injection site redness (erythema)
  • Headache, sleepiness (somnolence)
  • Muscular pain (myalgia)
  • Vomiting
  • Loss of appetite
  • Inconsolable crying
  • Injection site swelling
  • Injection site reactions (hardening of skin [induration], bruising, localised swelling filled with blood [haematoma], bleeding)
  • Urticaria (itchy rash, hives, welts)
  • Injection site itching (pruritus)
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Adults
  • Viral infections
  • Throat pain (pharyngolaryngeal pain), shortness of breath (dyspnoea), runny nose (rhinorrhoea), cough, wheezing, nasal congestion.
Children
  • Upper respiratory tract infection
  • Viral infections
  • Rash, rash characterised by spot and bump (maculo-papular rash), changes in the colour of the skin after inflammatory reaction
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Imojev contains

Active ingredient
(main ingredient)
Japanese encephalitis virus, live, attenuated: 4.0 - 5.8 log PFU*
* Plaque Forming Unit
Other ingredients
(inactive ingredients)
mannitol, lactose monohydrate, glutamic acid, potassium hydroxide, histidine, human serum albumin, sodium chloride, water for injections.
No adjuvant or antimicrobial preservative is added.

Do not take this medicine if you are allergic to any of these ingredients.

What Imojev looks like

Each pack of Imojev contains

  • One vial containing a white to creamy white vaccine powder,
  • One vial containing clear diluent,
  • One disposable syringe with 2 separate needles.

Your doctor will inject the diluent into the vaccine vial to make the suspension for your injection. After the mixing, Imojev is a colourless to amber suspension.

Who distributes Imojev

Biocelect Pty Ltd
Level 29, 66 Goulburn Street,
Sydney NSW 2000 Australia

Tel: +61 2 7202 1444
Email: [email protected]
Website: www.biocelect.com

This leaflet was prepared March 2023.

Published by MIMS July 2023

BRAND INFORMATION

Brand name

Imojev

Active ingredient

Japanese encephalitis vaccine (live, attenuated, recombinant)

Schedule

S4

 

1 Name of Medicine

Japanese encephalitis virus (live, attenuated).

2 Qualitative and Quantitative Composition

Imojev is a monovalent, live attenuated viral vaccine. The virus was obtained via recombinant DNA technology. It is based on the 17D-204 yellow fever vaccine virus in which two genes have been replaced by the corresponding genes from Japanese encephalitis (JE) virus. These are the premembrane (prM) and envelope (E) coding sequences of the SA14-14-2 live attenuated JE vaccine virus. The immunising antigens are the prM and E proteins from the SA14-14-2 vaccine virus.

After reconstitution.

Active ingredients:
Live, attenuated, recombinant Japanese encephalitis virus*: 4.0 - 5.8 log PFU**.
* Propagated in Vero cells.
** Plaque forming unit.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection and diluent.
The powder is a white to creamy white homogeneous cake which might be retracted from the sides of the vial. The diluent is a clear solution. After reconstitution, Imojev is a colourless to amber suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Imojev is indicated for prophylaxis of Japanese encephalitis caused by the Japanese encephalitis virus, in individuals from 9 months of age and over.

4.2 Dose and Method of Administration

Primary vaccination.

Individuals 9 months of age and over.

A 0.5 mL single injection of the reconstituted vaccine.

Booster.

Adult population (18 years of age and over).

There is no need for a booster dose up to 5 years after the administration of a single dose of Imojev.

Paediatric population (9 months to 17 years of age inclusive).

A booster dose of Imojev should be given after primary vaccination in order to confer long-term protection. The booster dose should be given preferably 12 months after primary vaccination and can be given up to 24 months after primary vaccination.
Imojev can also be given as a booster vaccination in children who were previously given an inactivated Japanese encephalitis (JE) vaccine for primary vaccination, in accordance with the recommended timing for the booster of the inactivated JE vaccine.
Safety and efficacy of a booster dose in children and adolescents 5 to 17 years of age have not been established. Nevertheless, the booster dose can be considered based on the available data in other age groups.
Once the freeze dried vaccine has been completely reconstituted using the diluent provided (see Section 4.2 Dose and Method of Administration, Instructions for use), it is administered via the subcutaneous route.
In individuals 2 years of age and over, the recommended injection site is the deltoid region of the upper arm.
In individuals between 9 and 24 months of age, the recommended injection site is the anterolateral aspect of the thigh or the deltoid region.
Do not administer by intravascular injection.
Imojev must not be mixed with any other injectable vaccine(s) or medicinal product(s).
Contact with disinfectants is to be avoided since they may inactivate the vaccine virus.
Product is for single use in one patient only. Discard any residue.

Instructions for use.

Using aseptic technique, Imojev vaccine is reconstituted by injecting all the 0.4% sodium chloride solution into the vial of freeze dried vaccine, using the syringe and one of the needles provided in the carton. The vial is gently swirled. After complete dissolution, a 0.5 mL dose of the reconstituted suspension is withdrawn into this same syringe. For injection, the syringe is fitted with the second needle provided in the package.
The product should be used once reconstituted and must be discarded if it is not used within one hour of reconstitution.
After use, any remaining vaccine and container must be disposed of safely, preferably by heat inactivation or incineration, according to locally agreed procedures.

4.3 Contraindications

Imojev should not be administered to anyone with a history of severe allergic reaction to any component of the vaccine or after previous administration of the vaccine or a vaccine containing the same components or constituents.
Vaccination must be postponed in case of febrile or acute disease.
Congenital or acquired immune deficiency impairing cellular immunity, including immunosuppressive therapies such as chemotherapy, high doses of systemic corticosteroids given for 14 days or more.
Imojev must not be administered to individuals with symptomatic HIV infection or with asymptomatic HIV infection when accompanied by evidence of impaired immune function.
Imojev must not be administered to pregnant women (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Imojev must not be administered to breastfeeding women (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).

4.4 Special Warnings and Precautions for Use

Before the injection of any biological, the person responsible for administration must take all precautions known for the prevention of allergic or any other reactions. As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following administration of the vaccine.
In individuals who have a history of serious or severe reaction within 48 hours of a previous injection with a vaccine containing similar components, the course of the vaccination must be carefully considered.
Imojev should under no circumstances be administered intravascularly.

Protection.

As with any vaccine, vaccination with Imojev may not protect 100% of vaccinated individuals.

Special patient groups.

For patients following a treatment with high doses of systemic corticosteroids given for 14 days or more, it is advisable to wait for at least one month or more following the interruption of therapy before carrying out the vaccination until immune function has recovered.

Use in the elderly.

In clinical trials, the seroconversion rates and the safety profiles were similar in the elderly and adults after the administration of one dose of Imojev.

Paediatric use.

Imojev is not recommended in children below the age of 9 months.

Effects on laboratory tests.

Interference of Imojev with laboratory and/or diagnostic tests has not been studied.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant administration with other vaccine(s).

Separate injection sites and separate syringes should be used when other vaccines are concomitantly administered with Imojev (see Section 4.2 Dose and Method of Administration).
From 12 months of age, Imojev may be administered at the same time as vaccines against measles, mumps, or rubella, either stand alone or combined.
For children living in or travelling to areas where risk for measles is high, Imojev may be administered at the same time as measles vaccine, either stand alone or combined with mumps and/or rubella vaccines, from as early as 9 months of age.
Imojev may be administered to adults at the same time as the yellow fever vaccine.

Vaccine-drug interactions.

In the case of immunosuppressive therapy or corticosteroid therapy, see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use.
Administering the vaccine in individuals who have previously received immunoglobulins:
In order to avoid any neutralisation of the attenuated viruses contained in the vaccine, vaccination must not be performed within 6 weeks, and preferably not within 3 months of injection of immunoglobulins or blood products containing immunoglobulins, such as blood or plasma.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

A reproductive and developmental toxicity study in which female rabbits were subcutaneously administered the human dose of Imojev twice prior to mating showed no effects on female mating or fertility. No fertility data are available in humans.
(Category B2)
Developmental toxicity studies in which female rabbits were subcutaneously administered the human dose of Imojev twice prior to mating and three times during gestation, or once between gestation days 6 to 18, or once on postnatal day 15, showed no adverse effects on pregnancy, embryo-foetal development, parturition or postnatal development. Vaccine antigen specific antibodies were transferred to foetuses.
As with all live attenuated vaccines, pregnancy constitutes a contraindication (see Section 4.3 Contraindications).
There is a theoretical risk that a live vaccine virus can cross the placenta and infect the foetus. It is not known whether Imojev can cause foetal harm when administered to a pregnant woman.
Women of childbearing age should be advised not to become pregnant for 4 weeks after vaccination.
A developmental toxicity study in which female rabbits were subcutaneously administered the human dose of Imojev once between gestation days 6 to 18, or once on postnatal day 15, showed no effects on pup survival, growth and development.
It is not known whether this vaccine is excreted in human milk.
Imojev vaccination is contraindicated in breastfeeding women (see Section 4.3 Contraindications).
Studies with some other live, attenuated virus vaccines have shown that a lactating postpartum woman may secrete the virus in breast milk and transmit virus to a breastfed infant.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive or use machines have been performed.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials experience.

Data in adult populations. The safety of Imojev has been assessed in 8 randomised clinical trials in individuals over 18 years of age. During the development in the adult population, approximately 2,500 individuals received an injection of Imojev.
Safety evaluation was performed for all individuals during the first 4 weeks following vaccination and serious adverse reactions were collected during at least six months of follow-up after a single dose of Imojev.
The most frequently reported systemic reactions after the administration of Imojev vaccine were headache, fatigue, malaise and myalgia. All these reactions were as frequently reported as after the administration of the inactivated Japanese encephalitis (JE) comparator vaccine or a placebo.
The most frequently reported reaction at the injection site after the administration of Imojev vaccine was injection site pain. All the injection site reactions were less frequently reported than after the administration of the inactivated JE comparator vaccine and as frequently reported as after the administration of a placebo.
Local and systemic reactions are ranked within each system organ class, under headings of frequency, using the following convention: [very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), including isolated reports].
The following possibly related adverse events were reported during clinical trials within 30 days after vaccination:

General disorders and administration site conditions.

Very common: fatigue, malaise, injection site pain.
Common: feeling hot, chills, injection site erythema, injection site pruritus, injection site swelling, injection site bruising.
Uncommon: pyrexia.

Nervous system disorders.

Very common: headache.
Common: dizziness.

Musculoskeletal and connective tissue disorders.

Very common: myalgia.
Common: arthralgia.

Gastrointestinal disorders.

Common: diarrhoea, nausea, abdominal pain, vomiting.

Respiratory, thoracic and mediastinal disorders.

Common: pharyngolaryngeal pain, dyspnoea, rhinorrhoea, cough, wheezing, nasal congestion.

Skin and subcutaneous tissue disorders.

Common: rash.

Infections and infestations.

Rare: viral infections.
Table 1 summarises the possibly related adverse events (frequency ≥ 1.0%) that were reported during clinical trials within 30 days after the administration of a single dose of Imojev, of the two first doses and the third dose of the inactivated JE comparator vaccine and of the placebo doses.
Data in paediatric populations. The safety of Imojev in paediatric populations has been assessed in phase II and phase III clinical trials. Overall, approximately 2,200 children received at least one injection of Imojev in these studies.
In addition, 10,000 individuals between 9 months and 5 years of age received Imojev either primary or booster vaccination in a large scale phase IV safety trial aimed at identifying serious, rare adverse reactions (see Section 4.8 Adverse Effects (Undesirable Effects), Adverse reactions from postmarketing surveillance).
Results from 5 phase II and phase III clinical trials with similar methodology for recording safety data were included in an integrated analysis of safety. During these clinical trials approximately 2,200 individuals between 9 months and 5 years of age received an injection of Imojev (approximately 50 infants from 9 to 12 months old and 2,050 toddlers from 12 months not previously immunised with a JE vaccine, as well as 100 children previously immunised with a two dose regime of a JE vaccine).
Safety evaluation was performed for all individuals during the first 4 weeks following vaccination and serious adverse reactions were collected during at least six months of follow-up after a single dose of Imojev.
The most frequently reported systemic reactions were malaise, myalgia, fever, and headache in children (2 to 5 years); and irritability, appetite loss, crying and fever in infants and toddlers (9 to 24 months).
The most frequently reported reactions at the injection site after the administration of Imojev vaccine was injection site pain/ tenderness and injection site erythema.
These adverse events observed during paediatric clinical trials were generally of mild intensity and of short duration. The onset of systemic reactions was generally seen within 3 days after immunisation.
Table 2 summarises the solicited reactions that were reported during clinical trials after the administration of a single dose of Imojev or of a control vaccine.
Table 3 summarises the nonserious adverse reactions that were reported during clinical trials within 28 days after the administration of a single dose of Imojev or of a control vaccine.
Local and systemic reactions are ranked within each system organ class, under headings of frequency, using the following convention: [very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), including isolated reports].
The following related adverse events were reported during clinical trials within 28 days after vaccination:

General disorders and administration site conditions.

Very common: pyrexia, malaise, irritability, injection site pain/ tenderness, injection site erythema.
Common: injection site swelling.
Uncommon: injection site reactions (induration, bruising, haematoma, haemorrhage).
Rare: injection site pruritus.

Nervous system disorders.

Very common: headache, somnolence.

Musculoskeletal and connective tissue disorders.

Very common: myalgia.

Gastrointestinal disorders.

Very common: vomiting.

Metabolism and nutrition disorders.

Very common: appetite loss.

Infections and infestations.

Uncommon: upper respiratory tract infection.
Rare: viral infection.

Skin and subcutaneous tissue disorders.

Uncommon: urticaria.
Rare: rash, maculopapular rash, postinflammatory pigmentation change.

Psychiatric disorders.

Very common: inconsolable crying.
No serious adverse events within 28 days of administration of Imojev were related to vaccination.
During the paediatric clinical trials, 29 cases of convulsions have been reported, including 28 cases of febrile convulsion and 1 case of convulsion without fever. All cases were assessed as not related to vaccination and were reported to be associated with concurrent infectious diseases (or common cold). In 9 cases, convulsions started within 30 days after Imojev vaccination.
In the following studies, the safety of Imojev presented no clinically relevant difference with the above described safety profile:
In a phase III trial in 390 individuals between 36 and 42 months of age (45 out of the 390 received a single dose of Imojev, and 345 out of the 390 received a second dose (booster dose) of Imojev 2 years after the first dose).
In a phase III trial in 119 children between 18 and 36 months of age who received a second dose (booster dose) of Imojev.

Adverse reactions from postmarketing surveillance.

No additional adverse reactions were identified from the phase IV safety trial conducted in 10,000 individuals between 9 months and 5 years of age, as well as from spontaneous reporting in postmarketing surveillance.
Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems (Australia).

4.9 Overdose

There is no specific information regarding overdose with Imojev.
For general advice on management of overdose, contact the Poisons Information Centre, telephone number 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: encephalitis vaccines, ATC code: J07BA.

Mechanism of action.

The vaccine is a live attenuated virus. Following administration, the virus replicates locally and elicits neutralising antibodies and cell mediated immune responses that are specific to the Japanese encephalitis (JE) virus. Available results indicate that protection is mainly mediated by neutralising antibodies.
In nonclinical studies, all animals that received a single dose of the vaccine developed specific neutralising antibodies against JE virus and were protected against infection by a virulent JE virus experimental challenge.

Clinical trials. Immunogenicity.

Passive antibody transfer results in a small animal model indicate that protection is mediated by neutralising antibodies and that the threshold for protection is a plaque reduction neutralisation titre of 1:10.
Immunogenicity data in adult populations. A single dose administration of Imojev is as immunogenic as a three dose regimen of an inactivated Japanese encephalitis (JE) comparator vaccine administered in adults 18 years of age and over.
A seroprotective level of antibodies is generally reached 14 days after vaccination.
In a randomised comparative phase III trial, 410 individuals over 18 years of age received a single dose of not less than 4.0 log PFU/dose of 0.5 mL of Imojev and 410 individuals over 18 years of age received a three dose regimen of 1 mL of an inactivated JE comparator vaccine.
Thirty days after vaccination, the seroprotection rates for the individuals who received Imojev were approximately 99% when measured against the homologous virus strain. These results are noninferior to those observed after the three dose regimen of the inactivated JE comparator vaccine.
Fourteen days after a single dose of Imojev, approximately 93% of the vaccinees showed seroprotective levels of neutralising antibodies.
Table 4 shows the seroprotection rates measured against the homologous virus strain, 14 and 30 days after vaccination with a single dose of Imojev or a three dose regimen of the inactivated JE comparator vaccine.
Neutralising antibody levels were also assessed against a panel of wild type strains belonging to the four main genotypes and originating from different countries. In a phase II trial, approximately 89% of vaccinees showed neutralising antibody levels above the 1:10 threshold against the tested wild type strains, 28 days after a single dose administration of Imojev.
In a long-term follow-up assessment in a randomised control phase II trial, 97.6% (95% CI, 93.3; 98.8) of individuals showed seroprotective levels six months after a single administration of Imojev. The probability of being still seroprotected 60 months after vaccination for those who were seroprotected at six months is 86.8%.
Long-term immunogenicity data up to month 60 are presented as Kaplan-Meier estimates in Table 5.
No long-term immunogenicity data beyond 5 years after the administration of a single dose of Imojev are available.
Immunogenicity data in paediatric populations.

Primary vaccination. Immune response 28 days after a single dose administration of Imojev.

A seroprotective level of antibodies is generally reached 28 days after vaccination.
A single dose administration of Imojev in 2 randomised trials in 1,231 toddlers (12 to 24 months) not previously immunised with a Japanese encephalitis (JE) vaccine showed that approximately 95% of individuals seroconverted and were seroprotected (neutralising antibody level above the threshold of protection) after 28 days.
Table 6 shows the immune response against the homologous virus strain, 28 days after vaccination with a single dose of Imojev.
In addition, approximately 96% of a subset of toddlers not previously immunised with a JE vaccine in a phase II trial seroconverted to three of the four tested JE wild type strains 28 days after a single dose administration of Imojev and approximately 70% seroconverted to the fourth strain.
A single dose administration of Imojev in a randomised comparative phase III trial in infants and toddlers (9 to 18 months) (N = 126) not previously immunised with a JE vaccine showed more than 99% of individuals seroconverted and were seroprotected after 28 days. These results were noninferior to those observed after the administration of a live attenuated Japanese encephalitis comparator vaccine. See Table 7.

Immune response up to 5 years after a single dose administration of Imojev.

The persistence of seroprotection was assessed in a phase II and a phase III trial in toddlers.
In the phase II trial, approximately 59% of toddlers who did not receive any JE vaccine before the single dose administration of Imojev were shown to still have seroprotective antibody levels 5 years after the vaccination.
Table 8 shows the immune response up to 5 years after vaccination with a single dose of Imojev.
In the phase III trial, approximately 67% of toddlers who did not receive any JE vaccine before the single dose administration of Imojev are still seroprotected 5 years after the vaccination. All the toddlers included in this trial with serological data available 28 days after the vaccination were seroprotected at this time point.
Table 9 shows the immune response against the homologous virus strain, up to 5 years after vaccination with a single dose of Imojev.
In another phase III trial in infants and toddlers (9 to 18 months) not previously immunised with a JE vaccine, approximately 88% of individuals were still seroprotected 1 year after the single dose administration of Imojev. See Table 10.

Booster. Booster dose of Imojev after primary vaccination with Imojev.

In a phase III trial, a second dose (booster dose) of Imojev was administered in children (36 to 42 months of age) (N = 340) 24 months after primary vaccination with Imojev. A control group of children (36 to 42 months of age) (N = 39) who never received a JE vaccine, received Imojev for the first time to characterise the primary response to Imojev.
The geometric mean titre (GMT) increased by nearly 6 fold from day 0 to day 7 after the administration of Imojev in children previously vaccinated. By comparison, the GMT did not increase in the control group, thus demonstrating an anamnestic response in the booster group. The GMT increased by nearly 57 fold from day 0 to day 28 in the booster group.
100% of children previously vaccinated with Imojev showed seroprotective antibody titres 28 days after the administration of the booster dose 24 months after primary vaccination.
Table 11 shows the immune response against the homologous virus strain, 7 and 28 days after administration of a booster dose of Imojev.
In a phase III trial, a second dose (booster dose) of Imojev was administered in children (2 to 4 years of age) (N = 97) between 12 and 24 months after primary vaccination with Imojev.
The GMT increased by nearly 51-fold from day 0 to day 28 in the booster group.
100% of children previously vaccinated with Imojev showed seroprotective antibody titres 28 days after the administration of the booster dose between 12 and 24 months after primary vaccination. See Table 12.
In the long-term follow-up assessment of the phase III trial, nearly all children (98.2%) who received the booster dose of Imojev 24 months after primary vaccination are still seroprotected 4 years after the vaccination.
Table 13 shows the immune response up to 4 years after vaccination with a booster dose of Imojev.

Booster vaccination with Imojev after the administration of an inactivated JE vaccine as a primary immunisation.

In a phase II trial, Imojev was administered to children (N = 97) (2 to 5 years) 6 to 38 months after a two dose primary vaccination with an inactivated JE vaccine (mouse brain derived JE vaccine).
The GMT increased by nearly 59-fold from day 0 to day 28.
Approximately 93% of individuals seroconverted and they were all seroprotected (titre above a threshold considered as protective) 28 days after the administration of Imojev.
Table 14 shows the immune response 28 days after the administration of a booster dose of Imojev after a primary vaccination with an inactivated JE vaccine.
In addition, approximately 99% of children showed seroprotective antibody levels against JE wild type strains belonging to the four main genotypes, 28 days after the administration of Imojev.
In the long-term follow-up assessment of the phase II trial, nearly all children (96.3%) who received the booster dose of Imojev 6 to 38 months after the two dose primary vaccination with the inactivated JE vaccine are still seroprotected 5 years after the vaccination.
Table 15 shows the immune response up to 5 years after the administration of a booster dose of Imojev after a primary vaccination with an inactivated JE vaccine.

5.2 Pharmacokinetic Properties

No pharmacokinetic studies have been performed.

5.3 Preclinical Safety Data

Genotoxicity.

Imojev has not been tested for genotoxic potential.

Carcinogenicity.

Imojev has not been tested for carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Mannitol, lactose monohydrate, glutamic acid, potassium hydroxide, histidine, human serum albumin, sodium chloride, water for injections.
No adjuvant or antimicrobial preservative is added.

6.2 Incompatibilities

Imojev must not be mixed with any other injectable vaccine(s) or medicinal product(s).

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the vials in the outer carton in order to protect from light.

6.5 Nature and Contents of Container

One dose of freeze-dried vaccine and one dose of diluent in separate vials (type I glass), each equipped with a stopper (halo-butyl) and a flip off cap (aluminium/polypropylene), with one syringe (polypropylene) and two needles (stainless steel). Pack size of 1 powder vial and 1 diluent vial, 1 syringe and 2 needles.

6.6 Special Precautions for Disposal

After use, any remaining vaccine and container must be disposed of safely, preferably by heat inactivation or incineration, according to locally agreed procedures.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes