Consumer medicine information

Varivax Refrigerated

Varicella zoster vaccine, live attenuated

BRAND INFORMATION

Brand name

Varivax Refrigerated

Active ingredient

Varicella zoster vaccine, live attenuated

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Varivax Refrigerated.

SUMMARY CMI

VARIVAX® Refrigerated

Consumer Medicine Information (CMI) summary

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

1. Why is my child or I being given VARIVAX Refrigerated?

VARIVAX Refrigerated is a vaccine used to help prevent chickenpox (varicella). It can be given to children 12 months of age and older, teenagers and adults who are healthy.
For more information, see Section 1. Why is my child or I being given VARIVAX Refrigerated? in the full CMI.

2. What should I know before my child or I are given VARIVAX Refrigerated?

Do not receive VARIVAX Refrigerated if you or your child have ever had an allergic reaction to VARIVAX Refrigerated or any of the ingredients listed at the end of the CMI.
Talk to your doctor if you or your child 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 my child or I are given VARIVAX Refrigerated? in the full CMI.

3. What if my child or I are taking other medicines?

Some medicines may interfere with VARIVAX Refrigerated and affect how it works. A list of these medicines is in Section 3. What if my child or I am taking other medicines? in the full CMI.

4. How is VARIVAX Refrigerated given?

  • The usual dose of VARIVAX Refrigerated is 0.5 mL. The dose of the vaccine is the same for everyone.
  • VARIVAX Refrigerated is given as an injection just under the skin (subcutaneously) of the upper arm by a doctor or trained nurse.

More instructions can be found in Section 4. How is VARIVAX Refrigerated given? in the full CMI.

5. What should I know after my child or I are given VARIVAX Refrigerated?

Things you should do
  • If you are 13 years of age or older, or your doctor tells you to have a second dose, keep your follow-up appointment with your doctor or clinic.
  • If you are a woman of child-bearing age, avoid falling pregnant for 3 months after vaccination
Things you should not do
  • Do not take aspirin or other salicylate medicines for six weeks after being given VARIVAX Refrigerated.
Driving or using machines
  • VARIVAX Refrigerated should not normally interfere with your ability to drive a car or operate machinery. However, VARIVAX Refrigerated may cause tiredness or dizziness in some people.
  • Be careful driving or operating machinery until you know whether VARIVAX Refrigerated has affected you.
Looking after your medicine
  • It is unlikely that you would be asked to store VARIVAX Refrigerated. If you are, keep it in the refrigerator, but not in the door compartment, until ready to use.
  • VARIVAX Refrigerated is stable for up to 24 months when stored in the refrigerator.

For more information, see Section 5. What should I know after my child or I are given VARIVAX Refrigerated? in the full CMI.

6. Are there any side effects?

Common side effects include: pain, soreness, swelling, itching, redness, bruising, numbness, stiffness or a hard lump where you had the injection, fever, tingling of the skin, irritability, swollen glands typically located in the neck, armpit or groin.
Serious side effects include: seizures or fits, severe skin conditions, skin infections, allergic reactions, bruising more easily than normal, red or purple, flat, pinhead spots under the skin; severe paleness, nausea, vomiting, chickenpox, difficulty walking. For a complete list of side effects and 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

VARIVAX® Refrigerated

Active ingredient: Varicella virus vaccine live (live varicella vaccine)

Consumer Medicine Information (CMI)

This leaflet provides important information about using VARIVAX Refrigerated. 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 VARIVAX Refrigerated.

Where to find information in this leaflet:

1. Why is my child or I being given VARIVAX Refrigerated?
2. What should I know before my child or I are given VARIVAX Refrigerated?
3. What if my child or I are taking other medicines?
4. How is VARIVAX Refrigerated given?
5. What should I know after my child or I are given VARIVAX Refrigerated?
6. Are there any side effects?
7. Product details

1. Why is my child or I being given VARIVAX Refrigerated?

VARIVAX Refrigerated is a vaccine used to help prevent chickenpox (varicella). It can be given to children 12 months of age and older, teenagers and adults who are healthy.

After vaccination with VARIVAX Refrigerated, most people will produce enough antibodies against the varicella virus. However, as with all vaccines, 100% protection against chickenpox cannot be guaranteed.

The chance of a severe reaction from VARIVAX Refrigerated is very small, but the risks from not being vaccinated are very serious.

What is chickenpox

Chickenpox is an infectious disease caused by the varicella-zoster virus, or otherwise known as varicella virus. It occurs in millions of people around the world each year, most often in children 5 to 9 years of age. Chickenpox is easily passed from one person to another. It is commonly spread from person to person through the air by sneezing or coughing. Once a person is infected, it usually takes about 2 to 3 weeks before symptoms of the infection start.

Symptoms of chickenpox include mild headache, moderate fever and general discomfort. These are followed by a rash of itchy, little red spots which usually start on the chest, stomach or back, but can appear anywhere on the body. There may be only a few spots or groups of spots, or even hundreds of spots that develop over the next 3 to 5 days. The spots will change into clear blisters filled with fluid which then become cloudy, break open, dry, scab and heal, usually within 5 to 20 days.

Although chickenpox is generally a fairly harmless infection, it may be associated with serious complications and/or rarely death. In children, the most common complications are bacterial skin infections. Less frequent but very serious complications include pneumonia, inflammation of the brain (encephalitis), Reye syndrome (which causes brain and liver damage), and death. Severe disease and serious complications are more likely to occur in teenagers and adults.

It is not known whether VARIVAX Refrigerated will prevent chickenpox if it is given after you have been exposed to the natural varicella virus. Therefore, vaccination before way exposure is the best to help protect against infection and possible serious complications.

Groups of people who would particularly benefit from being vaccinated with VARIVAX Refrigerated include those who have not been infected with chickenpox before and either:

  • work in jobs where they are at high risk of being infected,
  • are parents of young children, or
  • live in the same household as someone who has a poor immune system (such as people with organ transplants, certain cancers, and HIV/AIDS) and has not had chickenpox before.

How does it work

VARIVAX Refrigerated contains a weakened strain of living varicella virus. This strain of live virus causes either mild or no symptoms of infection.

VARIVAX Refrigerated works by causing your body to produce its own protection against chickenpox. It does this by making disease-fighting substances called antibodies to fight the varicella virus. If a vaccinated person comes into contact with live virus, the body is usually ready to destroy it.

Your doctor will use the official recommendations to decide the number of doses needed and when to get them. At least one injection of VARIVAX Refrigerated is needed to help protect against chickenpox in children aged 12 months to 12 years. In persons aged 13 years and older, a second injection is required after the first injection.

After vaccination with VARIVAX Refrigerated, most people will produce enough antibodies against the varicella virus. However, as with all vaccines, 100% protection against chickenpox cannot be guaranteed.

The chance of a severe reaction from VARIVAX Refrigerated is very small, but the risks from not being vaccinated are very serious.

2. What should I know before my child or I are given VARIVAX Refrigerated?

Warnings

Do not receive VARIVAX Refrigerated if:

  • you or your child have an allergy to VARIVAX Refrigerated or any of the ingredients listed at the end of this leaflet
  • you or your child have a serious allergy to the antibiotic, neomycin
    Symptoms of an allergic reaction may include swelling of the face, lips, tongue, throat, difficulty in breathing, or hives.
  • you or your child are pregnant or intend to become pregnant
  • you or your child are being treated with medicines which decrease the body's immune system such as corticosteroids (e.g., prednisone), cyclosporin or cancer medicines
  • you or your child have diseases which decrease the body's immune system, such as blood disorders, cancers of the blood cells or lymph system (e.g. leukaemia, lymphoma) and HIV/AIDS
  • you or your child have a family history of immune deficiency
  • you or your child have tuberculosis (TB) which is not being currently treated
  • you or your child have an infection with a high temperature

If you are not sure whether you or your child should be given VARIVAX Refrigerated, talk to your doctor.

Check with your doctor if you or your child:

  • are breast-feeding or plan to breast-feed
  • have or have had any serious medical conditions
  • have received blood or plasma transfusions or immune globulins within the past five months
    Your doctor may decide to delay your injection of VARIVAX Refrigerated.
  • have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.
    If you have not told your doctor about any of the above, tell them before you are given an injection of VARIVAX Refrigerated.

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

VARIVAX Refrigerated is not recommended to be given to pregnant women. Also women of child-bearing age should avoid becoming pregnant for 3 months after vaccination.

Check with your doctor if you or your child are pregnant or intend to become pregnant.

Breastfeeding

It is not known whether VARIVAX Refrigerated passes into breast milk. Your doctor will discuss the possible risks and benefits of being given VARIVAX Refrigerated when breast-feeding.

Talk to your doctor if you or your child are breastfeeding or intend to breastfeed.

Children

Do not give VARIVAX Refrigerated to children under 12 months of age.

The safety and effectiveness of VARIVAX Refrigerated in children below the age of 12 months have not been established.

Close Contact with High Risk People

In rare circumstances, it is possible to catch chickenpox, including severe chickenpox, from a person who has been vaccinated with VARIVAX Refrigerated. This may occur in persons who have not previously been vaccinated or had chickenpox, as well as persons who fall into one of the following categories:

  • individuals with a weakened immune system
  • pregnant women who never had chickenpox
  • newborn babies whose mothers never had chickenpox.

Whenever possible, individuals who have been vaccinated with VARIVAX Refrigerated should attempt to avoid close contact, for up to 6 weeks following the vaccination, with anyone who falls into one of the categories above. Tell your doctor if there is anyone who falls into one of the categories above and is expected to be in close contact with the person being vaccinated.

3. What if my child or I are taking other medicines?

Tell your doctor, nurse or pharmacist if you or your child have been given any other vaccines or 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.

VARIVAX Refrigerated should not be given to people who are using the following:

  • medicines that decrease the immune system, such as corticosteroids (e.g., prednisone) cyclosporin, or cancer medicines
  • aspirin or other salicylate medicines.

Talk to your doctor if you or your child are taking any of these medicines.

Some medicines should not be used for 6 to 8 weeks after receiving VARIVAX Refrigerated. These include:

  • aspirin or other salicylates.
    A serious condition called Reye Syndrome has been reported following the use of aspirin or other salicylate medicines during a natural chickenpox infection. Therefore, aspirin or other salicylates should be avoided for 6 weeks following vaccination with VARIVAX Refrigerated.
  • immune globulins.
    Your doctor will discuss with you the possible risks and benefits of having immune globulin injections in the 2 months following vaccination with VARIVAX Refrigerated.

Use with other vaccines

VARIVAX Refrigerated can be given at the same time as M-M-R II (measles, mumps and rubella virus vaccine live), oral polio vaccine, and diphtheria, tetanus and pertussis vaccine. The injections should be given at different places on the body and using separates syringes. Your doctor will decide if VARIVAX Refrigerated should be given with other vaccines.

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

4. How is VARIVAX Refrigerated given?

How much is given

The usual dose of VARIVAX Refrigerated is 0.5 mL. The dose of the vaccine is the same for everyone.

VARIVAX Refrigerated can be given to persons 12 months of age and older. For children aged 12 months to 12 years, at least one injection is given. Your doctor will use the official recommendations to decide the number of doses needed and when to get them.

For persons who are first vaccinated at 13 years of age and older, a second injection should be given 4 to 8 weeks after the first injection.

How is VARIVAX Refrigerated given

VARIVAX Refrigerated is given as an injection just under the skin (subcutaneously) of the upper arm by a doctor or trained nurse.

The vaccine should not be injected directly into veins (intravenously).

5. What should I know after my child or I are given VARIVAX Refrigerated?

Things you should do

If you are 13 years of age or older, or your doctor tells you to have a second dose, keep your follow-up appointment with your doctor or clinic.

It is important to have your follow-up injection of VARIVAX Refrigerated at the appropriate time to make sure the vaccine has the best chance of providing protection against the chickenpox virus.

If you are a woman of child-bearing age, avoid falling pregnant for 3 months after vaccination.

If you are about to be injected with any immune globulin (including varicella zoster globulin) and you have been injected with VARIVAX Refrigerated within the past 2 months, tell your doctor.

If you or your child have been given VARIVAX Refrigerated, avoid coming into contact, for six weeks, with a person who falls into one of the following categories:

  • people with a weakened immune system
  • pregnant women who have never had chickenpox
  • newborn babies whose mothers have never had chickenpox

These people may be at risk of catching chickenpox from you or your child.

Things you should not do

Do not take aspirin or other salicylate medicines for six weeks after being given VARIVAX Refrigerated.

A serious condition called Reye Syndrome has been reported following the use of aspirin or other salicylate medicines during a natural chickenpox infection.

Driving or using machines

Be careful driving or operating machinery until you know whether VARIVAX Refrigerated has affected you.

VARIVAX Refrigerated should not normally interfere with your ability to drive a car or operate machinery. However, VARIVAX Refrigerated may cause tiredness or dizziness in some people.

Make sure you know how you react to VARIVAX Refrigerated before you drive a car, operate machinery, or do anything else that could be dangerous if you are tired.

Looking after your vaccine

It is unlikely that you will be asked to store VARIVAX Refrigerated. However if you need to store VARIVAX Refrigerated:

  • Keep it where children cannot reach it.
  • Keep it in the refrigerator, but not in the door compartment.
  • Do not freeze VARIVAX Refrigerated

VARIVAX Refrigerated is stable for up to 24 months when stored in the refrigerator.

Keep the injection in the original pack until it is time for it to be given.

6. Are there any side effects?

VARIVAX Refrigerated helps protect most people from chickenpox, but it may have unwanted side effects in a few people.

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, nurse or pharmacist if you have any further questions about side effects.

Common side effects

Common side effectsWhat to do
  • pain, soreness, swelling, itching, redness, bruising, numbness, stiffness or a hard lump where you had the injection
  • fever
  • tingling of the skin
  • irritability
  • swollen glands typically located in the neck, armpit or groin
  • chickenpox-like rash on the body or at the injection site

These are the more common side effects of VARIVAX Refrigerated. For the most part these have been mild.

Speak to your doctor if you or your child have any of these common side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • seizures or fits
  • severe skin conditions
  • skin infections
  • allergic reactions
  • bruising more easily than normal, red or purple, flat, pinhead spots under the skin; severe paleness
  • nausea
  • vomiting
  • chickenpox
  • difficulty walking
  • shingles (herpes zoster)#, an infection which causes blisters and severe pain
  • drooping eyelid or sagging muscles on one side of the face, also called Bell's palsy
  • fever, chills, shortness of breath, cough, phlegm, difficulty breathing, wheezing which may be symptoms of pneumonia or pneumonitis
  • inflammation of the brain (encephalitis# - symptoms include headache and fever, progressing to hallucinations, confusion, paralysis of part or all of the body, disturbances of behaviour, speech and eye movements, stiff neck, and sensitivity to light)
  • inflammation of the coverings of the brain and spinal cord (meningitis)#
  • stroke

#Can be from naturally occurring chickenpox or the vaccine in healthy individuals or individuals with lowered immunity.

These may be serious side effects. You may need urgent medical attention. Serious side effects are rare.

As with all vaccines given by injection, there is a very small risk of a serious allergic reaction.

  • skin rash, itchiness, or other severe skin reactions
  • pinkish, itchy swellings on the skin, also called hives
  • swelling of the face, lips, mouth, throat or neck which may cause difficulty in swallowing or breathing

These are serious side effects. If you have them, you may have had a serious allergic reaction to VARIVAX Refrigerated. You may need urgent medical attention or hospitalisation. Most of these side effects occur within the first few hours of vaccination.

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, nurse or pharmacist if you notice anything else that may be making you or your child 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 vaccine.

7. Product details

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

What VARIVAX Refrigerated contains

Active ingredient
(main ingredient)		A minimum of 1350 PFU (plaque forming units) of Oka/Merck varicella virus (which is the weakened strain of varicella virus) when reconstituted with the diluent and stored at room temperature for 150 minutes (2 and a half hours).
Other ingredients
(inactive ingredients)		sucrose
hydrolysed porcine gelatin*
sodium chloride
monosodium glutamate monohydrate
dibasic sodium phosphate
monobasic potassium phosphate
potassium chloride
urea
*contains sulfites
Potential allergensneomycin

Each dose contains trace amounts of bovine (beef) serum.

The manufacture of this product includes exposure to bovine derived materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

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

What VARIVAX Refrigerated looks like

VARIVAX REFRIGERATED is a white powder that comes in a glass vial. It is reconstituted with a special diluent (water for injections) to make a solution suitable for injection.

Australian Register Numbers:

VARIVAX REFRIGERATED varicella virus vaccine live powder for injection vial (AUST R 90140)

VARIVAX REFRIGERATED varicella virus vaccine live powder for injection vial with prefilled diluent syringe (AUST R 115008)

VARIVAX REFRIGERATED varicella virus vaccine live powder for injection vial with sterile diluent vial (AUST R 337387)

Who sponsors VARIVAX Refrigerated

Merck Sharp & Dohme (Australia) Pty Limited
Level 1, Building A, 26 Talavera Road
Macquarie Park NSW 2113

Who distributes VARIVAX Refrigerated

Seqirus (Australia) Pty Ltd
Melbourne, Victoria
Australia

This leaflet was prepared in July 2023.

(S-WPPI-V210-I-ref-032023)

RCN: 000025626-AU

Copyright © 2023 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.

Published by MIMS September 2023

BRAND INFORMATION

Brand name

Varivax Refrigerated

Active ingredient

Varicella zoster vaccine, live attenuated

Schedule

S4

 

Notes

Distributed by Seqirus (Australia) Pty Ltd

1 Name of Medicine

Live varicella vaccine.

2 Qualitative and Quantitative Composition

Varivax Refrigerated [varicella virus vaccine live (Oka/Merck)] is a lyophilised preparation of the Oka/Merck strain of live, attenuated varicella virus. The virus was initially obtained from a child with wild type varicella, then introduced into human embryonic lung cell cultures, adapted to and propagated in embryonic guinea pig cell cultures, and finally propagated in human diploid cell cultures (WI-38). Further passage of the virus for varicella vaccine was performed at Research Laboratories of Merck Sharp and Dohme, LLC, Rahway, NJ, USA in human diploid cell cultures (MRC-5) that were free of adventitious agents.
Varivax Refrigerated, when reconstituted as directed, is a sterile preparation for subcutaneous administration. Each 0.5 mL dose contains a minimum of 1350 PFU (plaque forming units) of Oka/Merck varicella virus when reconstituted and stored at room temperature for 150 minutes (2½ hours).
Powder for Injection.
Varivax Refrigerated when reconstituted is a clear, colourless to pale yellow liquid.

List of excipients with known effect.

This vaccine may contain trace quantities of neomycin.
For the full list of excipients, see Section 6.1 List of Excipients.
The product also contains residual components of MRC-5 cells and trace quantities of neomycin, and bovine serum from MRC-5 culture media. The product contains no preservative.
The manufacture of this product includes exposure to bovine derived material. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

3 Pharmaceutical Form

See Section 2 Qualitative and Quantitative Composition.

4 Clinical Particulars

4.1 Therapeutic Indications

Varivax Refrigerated is indicated for vaccination against varicella in healthy individuals 12 months of age and older.
See the Australian Immunisation Handbook for vaccination recommendations and schedule.
Groups who would particularly benefit from vaccination include:
Non-immune adults, especially those in at risk occupations, such as healthcare workers, teachers and workers in children's day care centres;
Non-immune parents of young children;
Non-immune household contacts, both adults and children, of immunocompromised patients with no history of disease.

4.2 Dose and Method of Administration

For subcutaneous administration.
Varivax Refrigerated should not be administered intravenously or intradermally.
Children 12 months to 12 years of age should receive a 0.5 mL dose administered subcutaneously. A second dose of Varivax administered at least 3 months later is recommended to ensure optimal protection against varicella (see Section 5 Pharmacological Properties).
Adolescents and adults 13 years of age and older should receive a 0.5 mL dose administered subcutaneously at elected date and a second 0.5 mL dose 4 to 8 weeks later.
The outer aspect of the upper arm (deltoid) is the preferred site of injection.

Methods of administration.

The diluent should be stored separately at room temperature (20°C to 25°C, 68°F to 77°F) or in the refrigerator.

Vial of diluent.

To reconstitute the vaccine, first withdraw 0.7 mL of diluent into the syringe to be used for reconstitution. Inject all the diluent in the syringe into the vial of lyophilised vaccine and gently agitate to mix thoroughly. Withdraw the entire contents into a syringe and inject the total volume (about 0.5 mL) of reconstituted vaccine subcutaneously, preferably into the outer aspect of the upper arm (deltoid) or the anterolateral thigh.

Prefilled syringe of diluent.

To reconstitute the vaccine, inject the entire contents of the prefilled diluent syringe into the vial of lyophilised vaccine and gently agitate to mix thoroughly. Withdraw the entire contents into a syringe and inject the total volume (about 0.5 mL) of reconstituted vaccine subcutaneously, preferably into the outer aspect of the upper arm (deltoid) or the anterolateral thigh.
It is recommended that the vaccine be administered immediately after reconstitution, to minimise the loss of potency. Discard if reconstituted vaccine is not used within 150 minutes (2½ hours).

Caution.

A sterile syringe free of preservatives, antiseptics and detergents should be used for each injection and/or reconstitution of Varivax Refrigerated because these substances may inactivate the vaccine virus.
It is important to use a separate sterile syringe and needle for each patient to prevent transmission of infectious agents from one individual to another.
To reconstitute the vaccine, use only the diluent supplied (Sterile Diluent for Merck, Sharp and Dohme Live Virus Vaccines), since it is free of preservatives or other antiviral substances which might inactivate the vaccine virus.
Do not freeze reconstituted vaccine.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit.

4.3 Contraindications

A history of hypersensitivity to any component of the vaccine, including gelatin.
A history of anaphylactoid reaction to neomycin (each dose of reconstituted vaccine contains trace quantities of neomycin).
Individuals with blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.
Individuals receiving immunosuppressive therapy. Individuals who are on immunosuppressant drugs are more susceptible to infections than healthy individuals. Vaccination with live attenuated varicella vaccine can result in a more extensive vaccine associated rash or disseminated disease in individuals on immunosuppressant doses of corticosteroids.
Individuals with primary and acquired immunodeficiency states, including those who are immunosuppressed in association with AIDS or other clinical manifestations of infection with human immunodeficiency virus; cellular immune deficiencies; and hypogammaglobulinemic and dysgammaglobulinemic states.
A family history of congenital or hereditary immunodeficiency, unless the immune competence of the potential vaccine recipient is demonstrated.
Active untreated tuberculosis.
Any febrile respiratory illness or other active febrile infection.
Pregnancy; the possible effects of the vaccine on fetal development are unknown at this time. However, wild type varicella is known to sometimes cause fetal harm. If vaccination of postpubertal females is undertaken, pregnancy should be avoided for three months following vaccination (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).

4.4 Special Warnings and Precautions for Use

General.

Adequate treatment provisions should be available for immediate use should an anaphylactoid reaction occur.
The duration of protection from varicella infection with Varivax Refrigerated is unknown.
It is not known whether Varivax Refrigerated given immediately after exposure to wild type varicella virus will prevent illness.
The safety and efficacy of Varivax Refrigerated have not been established in children or young adults who are known to be infected with human immunodeficiency viruses with and without evidence of immunosuppression (also see Section 4.3 Contraindications).
Varivax Refrigerated should not be administered intravenously or intradermally. Varivax Refrigerated should not be mixed with other vaccines in the same syringe.

Transmission.

Postmarketing experience suggests that transmission of varicella vaccine virus (Oka/Merck) resulting in varicella infection including disseminated disease may occur rarely between vaccine recipients (who develop or do not develop a varicella-like rash) and contacts susceptible to varicella including healthy as well as high-risk individuals.
Therefore, vaccine recipients should attempt to avoid, whenever possible, close association with susceptible high risk individuals for up to six weeks. In circumstances where contact with high risk individuals is unavoidable, the potential risk of transmission of vaccine virus should be weighed against the risk of acquiring and transmitting wild type varicella virus. Susceptible high risk individuals include:
immunocompromised individuals;
pregnant women without documented history of varicella or laboratory evidence of prior infection;
newborn infants of mothers without documented history of varicella or laboratory evidence of prior infection.

Use in the elderly.

No data available.

Paediatric use.

No clinical data are available on safety or efficacy of Varivax Refrigerated in children less than one year of age. Administration to infants under 12 months of age is not recommended.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Vaccination should be deferred for at least 5 months following blood or plasma transfusions, or administration of immune globulin or varicella zoster immune globulin (VZIG).
Following administration of Varivax Refrigerated, any immune globulin including VZIG should not be given for 2 months thereafter, unless its use outweighs the benefits of vaccination.
Vaccine recipients should avoid use of salicylates for 6 weeks after vaccination with Varivax Refrigerated, as Reye syndrome has been reported following the use of salicylates during wild type varicella infection.
Results from clinical studies indicate that Varivax Refrigerated can be administered concomitantly with M-M-R II (Measles, Mumps and Rubella Virus Vaccine Live), diphtheria and tetanus toxoids and pertussis vaccine adsorbed and Haemophilus influenzae type b conjugate combined vaccine, or Haemophilus influenzae type b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) combined vaccine. If Varivax Refrigerated is not given concomitantly with M-M-R II, a 1-month interval between the 2 live virus vaccines should be observed. When varicella vaccine (Oka/Merck) was given 6 weeks after the combined vaccine of Haemophilus influenzae type b, diphtheria, tetanus and pertussis the GMT for varicella antibody was 14.5 gpELISA units compared with 10.5 for those given varicella vaccine (Oka/Merck) concomitantly with the combined vaccine of Haemophilus influenzae type b, diphtheria, tetanus and pertussis. There was little difference in seroconversion rates between the 2 groups. If Varivax Refrigerated is not given concomitantly with M-M-R II, a 1-month interval between the 2 live virus vaccines should be observed.
Limited data from an experimental product containing varicella vaccine suggest that Varivax Refrigerated can be administered concomitantly with DTaP (diphtheria, tetanus, acellular pertussis) and PedvaxHIB* [Haemophilus b conjugate vaccine (meningococcal protein conjugate)] using separate sites and syringes and with OPV (oral poliovirus vaccine).
*Not currently registered in Australia.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Varivax Refrigerated has not been evaluated for its potential to impair fertility.
(Category B2)
Currently available live attenuated virus vaccines have not caused teratogenic effects in humans. There are no adequate and well controlled studies in pregnant women. It is not known whether Varivax Refrigerated can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Therefore, Varivax Refrigerated should not be administered to pregnant females; furthermore, pregnancy should be avoided for three months following vaccination (see Section 4.3 Contraindications).
 It is not known whether varicella vaccine virus is secreted in human milk. Therefore, because some viruses are secreted in human milk, caution should be exercised if Varivax Refrigerated is administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Clinical studies.

In clinical trials, varicella vaccine (Oka/Merck) was administered to over 17,000 healthy children, adolescents and adults. Varicella vaccine (Oka/Merck) was generally well tolerated.
In a double blind placebo controlled study among 956 healthy children and adolescents, 914 of whom were serologically confirmed to be susceptible to varicella, the only adverse reactions that occurred at a significantly (p < 0.05) greater rate in vaccine recipients than in placebo recipients were pain and redness at the injection site and varicella-like rash.
Children 1 to 12 years of age.

One-dose regimen in children.

In clinical trials involving healthy children monitored for up to 42 days after a single dose of an earlier formulation of varicella vaccine (Oka/Merck), the frequency of fever, injection site complaints or rashes were reported as follows (see Table 1).
In addition, the most frequently (≥ 1%) reported adverse experiences, without regard to causality, are listed in decreasing order of frequency: upper respiratory illness, cough, irritability, fatigue, disturbed sleep, diarrhoea, loss of appetite, vomiting, otitis, headache, malaise, abdominal pain, other rash, nausea, chills, lymphadenopathy, myalgia, lower respiratory illness, allergic reactions (including allergic rash, hives), stiff neck, arthralgia, itching.
Pneumonitis has been reported rarely (< 1%) in children vaccinated with varicella vaccine (Oka/Merck); a causal relationship has not been established.
Febrile seizures have occurred rarely (< 0.1%) in children vaccinated with varicella vaccine (Oka/Merck); a causal relationship has not been established.
Clinical safety of refrigerator-stable varicella vaccine (Oka/Merck) (n = 635) was compared with that of the licensed frozen formulation of varicella vaccine (Oka/Merck) (n = 323) for 42 days postvaccination in US children 12 to 23 months of age. The safety profiles were comparable for the two different formulations. Pain/tenderness/soreness (24.8 to 28.9%) and erythema (18.4 to 21.0%) were the most commonly reported local reactions. The most common systemic adverse events (reported by ≥ 10% of subjects in one or more treatment groups, irrespective of causal relationship to vaccination) were: fever ≥ 38.9°C, oral equivalent (27.0 to 29.2%), upper respiratory infection (26.9 to 29.7%), otitis media (12.0 to 14.1%), cough (11.0 to 15.1%), rhinorrhea (8.7 to 10.6%), and irritability (6.5 to 11.9%). Six subjects reported serious adverse experiences; all were judged by the investigators as being unrelated to vaccination.

Two-dose regimen in children.

In a clinical trial involving healthy children who received two doses of varicella vaccine (Oka/Merck) 3 months apart and were monitored for up to 42 days after any dose, the frequency of fever, injection site complaints, rashes, and systemic clinical complaints are reported in Table 2. The 2-dose regimen of varicella vaccine was generally well tolerated, with a safety profile generally comparable to that of the 1-dose regimen.
Adolescents and adults 13 years of age and older. In clinical trials involving healthy adolescents and adults, the majority of whom received two doses of varicella vaccine (Oka/Merck) of an earlier formulation of the vaccine, and were monitored for up to 42 days after any dose, the frequency of fever, injection site complaints or rashes were reported as follows (see Table 3).
In addition, the most frequently (≥ 1%) reported adverse experiences without regard to causality, are listed in decreasing order of frequency: upper respiratory illness, headache, fatigue, cough, myalgia, disturbed sleep, nausea, malaise, irritability, diarrhoea, stiff neck, lymphadenopathy, chills, abdominal pain, loss of appetite, arthralgia, otitis, itching, vomiting, other rashes, lower respiratory illness, allergic reactions (including allergic rash, hives), and dizziness.

Post-marketing clinical studies.

In a post-marketing study conducted to evaluate short-term safety (follow-up of 30 or 60 days) in approximately 86,000 children, 12 months to 12 years of age and in approximately 3600 adolescents and adults, 13 years of age and older, varicella vaccine (Oka/Merck) was generally well tolerated. No serious vaccine related adverse events were reported.
As with any vaccine, there is the possibility that broad use of the vaccine could reveal adverse reactions not observed in clinical trials.

Post-marketing experience.

The following additional side effects have been reported regardless of causality since the vaccine has been marketed.

Body as a whole.

Anaphylaxis (including anaphylactic shock) and related phenomena such as angioneurotic oedema, facial oedema and peripheral oedema; anaphylaxis in individuals with or without an allergic history.

Eye disorders.

Necrotising retinitis (reported only in immunocompromised individuals).

Gastrointestinal disorders.

Nausea; vomiting.

Haemic and lymphatic system.

Aplastic anaemia; thrombocytopenia (including idiopathic thrombocytopenic purpura (ITP); lymphadenopathy.

Infections and infestations.

Varicella (vaccine strain).

Nervous/psychiatric.

Encephalitis*; cerebrovascular accident; Guillain-Barre syndrome; transverse myelitis; Bell's palsy; ataxia; paresthesia; aseptic meningitis; meningitis*; irritability; dizziness; febrile and nonfebrile seizures; syncope.

Respiratory.

Pharyngitis; pneumonia/pneumonitis; upper respiratory tract infection.

Skin.

Stevens-Johnson syndrome; erythema multiforme; Henoch-Schonlein purpura; secondary bacterial infections of the skin and soft tissue, including cellulitis; herpes zoster*.
*Cases caused by wild-type varicella or vaccine strain varicella have been reported in immunocompromised or immunocompetent individuals.

Reporting suspected adverse effects.

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.

4.9 Overdose

There are no data with regard to overdose.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

Epidemiology.

Varicella (chickenpox) is a highly communicable disease in children, adolescents and adults caused by the varicella zoster virus. The disease usually consists of 300 to 500 maculopapular and/or vesicular lesions accompanied by a fever (oral temperature ≥ 37°C) in up to 70% of individuals. Over the period 1993-94 to 1996-97, there has been an average of 73 hospitalisations per month with a principal diagnosis of varicella. Between 1991 and 1996, there was a total of 36 deaths from varicella in Australia. Varicella hospitalisation and deaths occur across all ages. 59% of hospitalisations and 39% of deaths from varicella were of children under 15 years (in the years with data available). The hospitalisation rate for varicella in children has remained consistently over 11 per 100,000 between 1993-94 and 1996-97. Death rates from varicella for children have ranged between 0.05 and 0.08 per 100,000 during the period 1991 to 1996. Although it is generally a benign, self limiting disease, varicella may be associated with serious complications (e.g. bacterial superinfection, pneumonia, encephalitis, Reye syndrome) and/or death.

5.1 Pharmacodynamic Properties

Mechanism of action.

Varicella vaccine (Oka/Merck) induces both humoral and cell-mediated immune responses in vaccinees. The relative contributions of humoral immunity and cell-mediated immunity to protection from varicella are unknown.

Clinical trials.

Evaluation of clinical efficacy afforded by Varivax.

The following section presents clinical efficacy data on a 1-dose regimen and a 2-dose regimen in children, and a 2-dose regimen in adolescents and adults.
Clinical data in children.

One-dose regimen in children.

In combined clinical trials of varicella vaccine (Oka/Merck) at doses ranging from 1,000 to 17,000 PFU, the majority of subjects who received varicella vaccine (Oka/Merck) and were exposed to wild type virus were either completely protected from varicella or developed a milder form (for clinical description see below) of the disease.
The protective efficacy of varicella vaccine (Oka/Merck) was evaluated in three different ways: 1) by comparing varicella rates over 7 to 9 years in vaccinees versus historical controls (efficacy 83 to 94%); 2) by assessment of protection from disease following household exposure over 7 to 9 years (efficacy 81 to 88%); and 3) by a placebo-controlled, double-blind clinical trial over 2 years (efficacy 95 to 100%).
Although no placebo-controlled trial was carried out with Varivax (Refrigerated) using the current formulation of the vaccine, a placebo-controlled trial was conducted using a formulation containing 17,000 PFU per dose. In this trial, a single dose of varicella vaccine (Oka/Merck) protected 95 to 100% of children against varicella over a two-year period. The study enrolled healthy individuals 1 to 14 years of age (n = 491 vaccine, n = 465 placebo). In the first year, 8.5% of placebo recipients contracted varicella, while no vaccine recipient did, for a calculated protection rate of 100% during the first varicella season. In the second year, when only a subset of individuals agreed to remain in the blinded study (n = 169 vaccine, n = 163 placebo), 95% protective efficacy was calculated for the vaccine group as compared with placebo.
In early clinical trials with an earlier formulation, a total of 4240 children 1 to 12 years of age received 1000 to 1625 PFU of attenuated virus per dose of varicella vaccine (Oka/Merck) and have been followed for up to 9 years post single-dose vaccination. In this group, there was considerable variation in varicella rates among studies and study sites, and much of the reported data were acquired by passive follow-up. It was observed that 0.3 to 3.8% of vaccinees per year reported varicella (called breakthrough cases). This represents an approximate 83% (95% confidence interval [CI], 82%, 84%) decrease from the age-adjusted expected incidence rates in susceptible subjects over this same period. In those who developed breakthrough varicella post-vaccination, the majority experienced mild disease (median of the maximum number of lesions < 50). In one study, a total of 47% (27/58) of breakthrough cases had < 50 lesions compared with 8% (7/92) in unvaccinated individuals, and 7% (4/58) of breakthrough cases had > 300 lesions compared with 50% (46/92) in unvaccinated individuals.
Among a subset of vaccinees who were actively followed in these early trials for up to 9 years post-vaccination, 179 individuals had household exposure to varicella. There were no reports of breakthrough varicella in 84% (150/179) of exposed children, while 16% (29/179) reported a mild form of varicella (38% [11/29] of the cases with a maximum total number of < 50 lesions; no individuals with > 300 lesions). This represents an 81% reduction in the expected number of varicella cases utilizing the historical attack rate of 87% following household exposure to varicella in unvaccinated individuals in the calculation of efficacy.
In later clinical trials with an earlier vaccine formulation, a total of 1114 children 1 to 12 years of age received 2900 to 9000 PFU of attenuated virus per dose of varicella vaccine (Oka/Merck) and have been actively followed for up to 10 years post single-dose vaccination. It was observed that 0.2 to 2.3% of vaccinees per year reported breakthrough varicella for up to 10 years post single-dose vaccination. This represents an estimated efficacy of 94% (95% CI, 93%, 96%), compared with the age-adjusted expected incidence rates in susceptible subjects over the same period. In those who developed breakthrough varicella post-vaccination, the majority experienced mild disease with the median of the maximum total number of lesions < 50. The severity of reported breakthrough varicella, as measured by number of lesions and maximum temperature, appeared not to increase with time since vaccination.
Among a subset of vaccinees who were actively followed in these later trials for up to 10 years post-vaccination, 95 individuals were exposed to an unvaccinated individual with wild-type varicella in a household setting. There were no reports of breakthrough varicella in 92% (87/95) of exposed children; while 8% (8/95) reported a mild form of varicella (maximum total number of lesions < 50; observed range, 10 to 34). This represents an estimated efficacy of 90% (95% CI, 82%, 96%) based on the historical attack rate of 87% following household exposure to varicella in unvaccinated individuals in the calculation of efficacy.
Among 9202 children ≤ 12 years of age who received 1 injection of varicella vaccine (Oka/Merck), there were 1149 cases of breakthrough varicella (occurring more than 6 weeks post-vaccination) of which 20 (1.7%) were classified as severe (≥ 300 lesions and a temperature ≥ 37.8°C oral). Compared with the proportion of severe cases (36%) from wild-type varicella infection in unvaccinated historical controls, this represents a 95% relative reduction in the proportion of severe cases among recipients of varicella vaccine who developed breakthrough varicella.

Two-dose regimen in children.

In a clinical trial, a total of 2216 children 12 months to 12 years of age with a negative history of varicella were randomised to receive either 1 dose of varicella vaccine (Oka/Merck) (n = 1114) or 2 doses of varicella vaccine (Oka/Merck) (n = 1102) given 3 months apart. Subjects were actively followed for varicella, any varicella-like illness, or herpes zoster and any exposures to varicella or herpes zoster on an annual basis for 10 years after vaccination. Persistence of varicella-zoster vaccine (VZV) antibody was measured annually for 9 years. Most cases of varicella reported in recipients of 1 dose or 2 doses of vaccine were mild. The estimated vaccine efficacy for the 10-year observation period was 94% for 1 dose and 98% for 2 doses (p < 0.001). This translates to a 3.4-fold lower risk of developing varicella > 42 days post-vaccination during the 10-year observation period in children who received 2 doses than in those who received 1 dose (2.2% vs. 7.5%, respectively).
There are an insufficient number of breakthrough varicella cases in vaccinated children to assess the rate of protection of varicella vaccine (Oka/Merck) against the serious complications of varicella (e.g. encephalitis, hepatitis, pneumonia).
Clinical data in adolescents and adults. Although no placebo-controlled trial was carried out in adolescents and adults, the protective efficacy of varicella vaccine (Oka/Merck) was calculated by evaluation of protection when vaccinees received 2 doses of an earlier formulation of varicella vaccine (Oka/Merck) 4 or 8 weeks apart and were subsequently exposed to varicella in a household setting over 6 to 7 years. In earlier clinical trials with up to 6 years of follow-up, 13 of the 76 individuals (17%) who had household exposure to varicella, developed varicella. All of the varicella cases that were reported were generally mild with a median of 37 lesions (range 8 to 75). In later clinical trials with up to 7 years of follow-up, none of 19 individuals (0%) who had household exposure developed varicella.
The attack rate of unvaccinated adults exposed to a single contact in a household has not been previously studied. If the attack rate of 87% following household exposure in susceptible children holds true for susceptible adolescents and adults, the estimated efficacy of the vaccine in the prevention of any varicella disease would range from 80 to 100%.
There are an insufficient number of breakthrough varicella cases among vaccinated adolescents and adults to assess the rate of protection of varicella vaccine (Oka/Merck) against the serious complications of varicella (e.g. encephalitis, hepatitis, pneumonia) and during pregnancy (congenital varicella syndrome).

Immunogenicity of varicella vaccine (Oka/Merck).

Clinical trials with several formulations of the vaccine containing attenuated virus ranging from 1000 to 50,000 PFU per dose have demonstrated that varicella vaccine (Oka/Merck) induces detectable humoral immune responses in a high proportion of individuals and is generally well tolerated in healthy individuals ranging from 12 months to 55 years of age.
The following section presents immunogenicity data on a 1-dose regimen and a 2-dose regimen in children, and a 2-dose regimen in adolescents and adults.

One-dose regimen in children.

Seroconversion as defined by the acquisition of any detectable varicella antibodies (based on assay cutoff that generally corresponds to 0.6 units in the gpELISA, a highly sensitive assay which is not commercially available) was observed in 98% of vaccinees at approximately 4 to 6 weeks post-vaccination in 9610 susceptible children 12 months to 12 years of age who received doses ranging from 1000 to 50,000 PFU. Rates of breakthrough disease were significantly lower among children with varicella antibody titres ≥ 5 gpELISA units compared to children with titres < 5 gpELISA units. Titres ≥ 5 gpELISA units were induced in approximately 83% of children vaccinated with a single dose of vaccine at 1000 to 50,000 PFU per dose. The immune response rate to varicella vaccine (Oka/Merck) (as determined by the percentage of subjects with varicella antibody titres ≥ 5 gpELISA units at 6 weeks post-vaccination, an approximate correlation of protection) in subjects participating in follow-up studies ranged from 72 to 98%.
Immunogenicity of refrigerator-stable varicella vaccine (Oka/Merck) (6550 PFU per dose, n = 320 and 28,400 PFU per dose, n = 315), was compared with that of the licensed frozen formulation (9189 PFU per dose, n = 323) in a double-blind, randomised, multicenter study in US children 12 to 23 months of age, all of whom received M-M-R II (Measles, Mumps, and Rubella Virus Vaccine Live) concomitantly. The per-protocol analysis included all subjects with prevaccination varicella antibody titres < 1.25 gpELISA units (n = 267 to 276 per group); the antibody responses were comparable across the 3 treatment groups, with 6-week postvaccination varicella antibody titres ≥ 5 gpELISA units in 93.3%, 93.8%, and 95.1% of subjects, respectively.

Two-dose regimen in children.

In a multicenter study, 2216 healthy children 12 months to 12 years of age received either 1 dose of varicella vaccine (Oka/Merck) or 2 doses administered 3 months apart. The immunogenicity results are shown in Table 4.
The results from this study and other studies in which a second dose of varicella vaccine (Oka/Merck) was administered 3 to 6 years after the initial dose demonstrate significant boosting of the VZV antibodies with a second dose. VZV antibody levels after 2 doses given 3 to 6 years apart are comparable to those obtained when the 2 doses are given 3 months apart.

Two-dose regimen in adolescents and adults.

In a multicenter study involving susceptible adolescents and adults 13 years of age and older, two doses of the earlier formulation of varicella vaccine (Oka/Merck) administered four to eight weeks apart induced a seroconversion rate (gpELISA ≥ 0.6 units) of approximately 75% in 539 individuals four weeks after the first dose and of 99% in 479 individuals four weeks after the second dose. The average antibody response in vaccinees who received the second dose eight weeks after the first dose was higher than that in those who received the second dose four weeks after the first dose. In another multicenter study involving adolescents and adults, two doses of the earlier formulation of varicella vaccine (Oka/Merck) administered eight weeks apart induced a seroconversion rate (gpELISA ≥ 0.6 units) of 94% in 142 individuals six weeks after the first dose and 99% in 122 individuals six weeks after the second dose.

Persistence of immune response.

The following section presents immune persistence data on a 1-dose regimen and a 2-dose regimen in children, and a 2-dose regimen in adolescents and adults.

One-dose regimen in children.

In those clinical studies involving healthy children who have been followed long-term post single-dose vaccination, detectable varicella antibodies (gpELISA ≥ 0.6 units) were present in 99.1% (3092/3120) at 1 year, 99.4% (1382/1391) at 2 years, 98.7% (1032/1046) at 3 years, 99.3% (997/1004) at 4 years, 99.2% (727/733) at 5 years, and 100% (432/432) at 6 years postvaccination.

Two-dose regimen in children.

Over 9 years of follow-up, the GMTs (geometric mean titre) and percent of subjects with VZV antibody titres ≥ 5 gpELISA units/mL in the 2-dose recipients were higher than those in the 1-dose recipients for the first year of follow-up and comparable during the entire follow-up period. The cumulative rate of VZV antibody persistence with both regimens remained very high at year 9 (99.0% for the 1-dose group and 98.8% for the 2-dose group).

Two-dose regimen in adolescents and adults.

In clinical studies involving healthy adolescents and adults who received 2 doses of vaccine, detectable varicella antibodies (gpELISA ≥ 0.6 units) were present in 97.9% (568/580) at 1 year, 97.1% (34/35) at 2 years, 100% (144/144) at 3 years, 97.0% (98/101) at 4 years, 97.5% (78/80) at 5 years, and 100% (45/45) at 6 years post-vaccination.
A boost in antibody levels has been observed in vaccinees following exposure to wild-type varicella which could account for the apparent long-term persistence of antibody levels after vaccination in these studies. The duration of protection from varicella obtained using varicella vaccine (Oka/Merck) in the absence of wild-type boosting is unknown.
Vaccination with Varivax (Refrigerated) may not result in protection of all healthy, susceptible children, adolescents, and adults.

Transmission.

In the placebo-controlled trial, transmission of vaccine virus was assessed in household settings (during the 8-week post-vaccination period) in 416 susceptible placebo recipients who were household contacts of 445 vaccine recipients. Of the 416 placebo recipients, three developed varicella and seroconverted, nine reported a varicella-like rash and did not seroconvert, and six had no rash but seroconverted. If vaccine virus transmission occurred, it did so at a very low rate and possibly without recognizable clinical disease in contacts. These cases may represent either wild-type varicella from community contacts or a low incidence of transmission of vaccine virus from vaccinated contacts. Post-marketing experience suggests that transmission of varicella vaccine virus (Oka/Merck) resulting in varicella infection including disseminated disease may occur rarely between vaccine recipients (who develop or do not develop a varicella-like rash) and contacts susceptible to varicella including healthy as well as high-risk individuals (see Section 4.4 Special Warnings and Precautions for Use, Transmission).

Herpes zoster.

Overall, 9543 healthy children (12 months to 12 years of age) and 1652 adolescents and adults (13 years of age and older) have been vaccinated with varicella vaccine (Oka/Merck) in clinical trials. Twelve cases of herpes zoster have been reported in children during 84,414 person years of follow-up in clinical trials, resulting in a calculated incidence of at least 14 cases per 100,000 person years. The completeness of this reporting has not been determined. Two cases of herpes zoster have been reported in the adolescent and adult age group during 12,372 person years of follow-up in clinical trials resulting in a calculated incidence of 16 cases per 100,000 person years.
All 14 cases of herpes zoster were mild and no sequelae were reported. Two cultures (one child and one adult) obtained from the vesicles were positive for wild-type varicella-zoster virus as confirmed by restriction endonuclease analysis. The long-term effect of varicella vaccine (Oka/Merck) on the incidence of herpes zoster, particularly in those vaccinees exposed to wildtype varicella, is unknown at present.
In children, the reported rate of zoster in vaccine recipients appears not to exceed that previously determined in a population-based study of healthy children who had experienced wild-type varicella. The incidence of zoster in adults who have had wild-type varicella infection is higher than that in children.

Reye syndrome.

Reye Syndrome has occurred in children and adolescents following wild-type varicella infection, the majority of whom had received salicylates. In clinical studies in healthy children and adolescents in the United States, physicians advised varicella vaccine recipients not to use salicylates for six weeks after vaccination. There were no reports of Reye Syndrome in varicella vaccine recipients during these studies.

Studies with other vaccines.

In combined clinical studies involving 1107 children 12 to 36 months of age, 680 received varicella vaccine (Oka/Merck) and M-M-R II (Measles, Mumps and Rubella Virus Vaccine Live) concomitantly at separate sites and 427 received the vaccines six weeks apart. Seroconversion rates and antibody levels were comparable between the two groups at approximately six weeks post-vaccination to each of the virus vaccine components. No differences were noted in adverse reactions reported in those who received varicella vaccine (Oka/Merck) concomitantly with M-M-R II at separate sites and those who received varicella vaccine (Oka/Merck) and M-M-R II at different times (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
In a clinical study involving 609 children 12 months to 23 months of age, 305 received varicella vaccine (Oka/Merck), M-M-R II (Measles, Mumps and Rubella Virus Vaccine Live), and Haemophilus influenzae type b, diphtheria, tetanus and pertussis combined vaccine concomitantly at separate sites and 304 received M-M-R II and Haemophilus influenzae type b, diphtheria, tetanus and pertussis combined vaccine given concomitantly followed by varicella vaccine (Oka/Merck) 6 weeks later. At six weeks post-vaccination, seroconversion rates for measles, mumps, rubella and varicella were similar between the two groups. Compared to prevaccination GMTs the six week post-vaccination boost in GMTs for Haemophilus influenzae type b, diphtheria, tetanus and pertussis was similar between the two groups. GMTs for all antigens were similar except for varicella which was lower when varicella vaccine (Oka/Merck) was administered concomitantly with M-M-R II and Haemophilus influenzae type b, diphtheria, tetanus and pertussis combined vaccine but within the range of GMTs seen in previous clinical experience when varicella vaccine (Oka/Merck) was administered alone. At 1 year postvaccination, GMTs for measles, mumps, rubella, varicella and Haemophilus influenzae type b were similar between the two groups. All three vaccines were well tolerated regardless of whether they were administered concomitantly at separate sites or 6 weeks apart. There were no clinically important differences in reaction rates when the three vaccines were administered concomitantly versus 6 weeks apart.
In a clinical study involving 822 children 12 to 15 months of age, 410 received Haemophilus influenzae type b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) combined vaccine, M-M-R II, and varicella vaccine (Oka/Merck) concomitantly at separate sites, and 412 received Haemophilus influenzae type b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) combined vaccine followed by M-M-R II and varicella vaccine (Oka/Merck) given concomitantly at separate sites, 6 weeks later. At 6 weeks post-vaccination, the immune responses for the subjects who received the concomitant injections of Haemophilus influenzae type b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) combined vaccine, M-M-R II, and varicella vaccine (Oka/Merck) were similar to those of the subjects who received Haemophilus influenzae type b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) combined vaccine followed 6 weeks later by M-M-R II and varicella vaccine (Oka/Merck) with respect to all antigens administered. All 3 vaccines were generally well tolerated regardless of whether they were administered concomitantly at separate sites or 6 weeks apart. There were no clinically important differences in reaction rates when the 3 vaccines were administered concomitantly versus 6 weeks apart.
Varivax (Refrigerated) is recommended for subcutaneous administration. However, during clinical trials, some children received varicella vaccine (Oka/Merck) intramuscularly resulting in seroconversion rates similar to those in children who received the vaccine by the subcutaneous route. Persistence of antibody and efficacy in those receiving intramuscular injections have not been defined.

5.2 Pharmacokinetic Properties

Absorption.

Not applicable.

Distribution.

Not applicable.

Metabolism.

Not applicable.

Excretion.

Not applicable.

5.3 Preclinical Safety Data

Genotoxicity.

Mutagenicity.

Varivax Refrigerated has not been evaluated for its mutagenic potential.

Carcinogenicity.

Varivax Refrigerated has not been evaluated for its carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Dibasic sodium phosphate, hydrolysed porcine gelatin*, monobasic potassium phosphate, monosodium glutamate monohydrate, potassium chloride, sodium chloride, sucrose, urea.
*Contains sulfites.

Diluent.

Water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Storage.

Vaccine vial.

During shipment, to ensure that there is no loss of potency, the vaccine must be maintained at a temperature of 2°C to 8°C or colder (36°F to 46°F or colder), but not exceed temperatures lower than -50°C (-58°F). Use of dry ice may subject Varivax to temperatures colder than -50°C (-58°F).
Immediately upon receipt of the vaccine shipment, the vaccine must be kept in the refrigerator at a temperature of 2°C to 8°C (36°F to 46°F) until ready for use. The vaccine should not be frozen.
Before reconstitution, Varivax Refrigerated has a shelf life of 24 months when refrigerated at 2°C to 8°C or colder (36°F to 46°F or colder).
Before reconstitution, protect from light.
Discard if reconstituted vaccine is not used within 150 minutes (2½ hours).

Prefilled syringe of diluent.

The diluent should be stored separately at room temperature (20°C to 25°C, 68°F to 77°F), or in the refrigerator.

Combination packs with the vaccine vial and vial of diluent or prefilled syringe of diluent.

For combination packs with the vaccine vial and diluent packaged together, store in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not store the combination pack in the freezer.

Stability.

Varivax Refrigerated has a minimum potency level of approximately 1350 PFU 150 minutes (2½ hours) after reconstitution at room temperature (20°C to 25°C, 68°F to 77°F).

6.5 Nature and Contents of Container

Varivax Refrigerated is supplied as:
(1) a single dose vial of lyophilised vaccine packed with a single vial of sterile diluent;
(2) a box of a single-dose vial of lyophilised vaccine packed with a single vial of sterile diluent;
(3) a box of 5 single-dose vial of lyophilised vaccine packed with 5 single vials of sterile diluent;
(4) a box of 10 single-dose vials of lyophilised vaccine;
(5) Sterile Diluent for Merck Sharp and Dohme Live Virus Vaccines is available in boxes of 10 vials;
(6) a box of 1 blister pack consisting of a single dose vial of lyophilised vaccine packed with a pre-filled syringe of sterile diluent;
(7) a box of 10 blisters packs each consisting of a single dose vial of lyophilised vaccine packed with a single pre-filled syringe of sterile diluent.
Not all presentations and packs sizes may be supplied.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Not applicable.

CAS number.

Not applicable.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes