Consumer medicine information

Priorix-Tetra

Varicella zoster vaccine, live attenuated; Rubella vaccine, live; Mumps vaccine, live; Measles vaccine, live

BRAND INFORMATION

Brand name

Priorix-Tetra Powder for injection

Active ingredient

Varicella zoster vaccine, live attenuated; Rubella vaccine, live; Mumps vaccine, live; Measles vaccine, live

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Priorix-Tetra.

WHAT IS IN THIS LEAFLET

This leaflet answers some of the common questions about PRIORIX-TETRA vaccine. It does not contain all the available information. It does not take the place of talking to your doctor, nurse or pharmacist.

All medicines and vaccines have risks and benefits. Your doctor has weighed the possible risks of you or your child having PRIORIX-TETRA against the expected benefits.

If you have any concerns about PRIORIX-TETRA talk to your doctor, nurse or pharmacist.

Keep this leaflet with this vaccine.

You may need to read it again.

WHAT PRIORIX-TETRA IS USED FOR

PRIORIX-TETRA is a vaccine used to prevent four diseases, measles, mumps, rubella (German measles) and varicella (chickenpox).

Measles, mumps, rubella and varicella are all infectious diseases caused by viruses. The vaccine works by causing the body to produce its own protection (antibodies) against these diseases.

Measles

Measles is a highly infectious viral illness. Measles is spread by small droplets from the nose, throat or mouth of an infected person (often before it is obvious they have measles). Measles often begins with a fever, runny nose, hacking cough and conjunctivitis (eye inflammation). The rash appears 3-5 days after the onset of symptoms and spreads rapidly all over the body. Measles is often a severe disease complicated by ear infection and pneumonia (lung infection). Encephalitis (swelling of the brain) can also occur and can sometimes result in permanent brain damage or death.

Unimmunised children in the following groups are at particular risk from severe measles infection:

  • children with chronic conditions such as cystic fibrosis, congenital heart or kidney disease, failure to thrive, Down's Syndrome
  • children from the age of 1 year upwards in child care centres, family day care and playgroups
  • children living in institutions
  • Aboriginal and Torres Strait Islander children.

Mumps

Mumps is an infectious viral disease spread by infected droplets of saliva. Symptoms often begin with chilly sensations, headache, loss of appetite, general unwellness and fever. The salivary glands on one or both sides of the face can then become very painful and swollen. Complications include meningoencephalitis (swelling around the brain) and in older patients the disease may involve other organs e.g. testes in males.

Rubella (German measles)

Rubella is generally a mild infectious viral illness spread by airborne droplets. It can cause mild fever, general unwellness, swollen glands and mild red rash. It often goes unnoticed in adolescents and adults. However rubella can cause miscarriage, stillbirth or birth defects in infants born to mothers infected with rubella during the early months of pregnancy.

Varicella (Chickenpox)

Chickenpox is a highly infectious disease, which usually causes an itchy, red rash with blisters. After about 1 week, most of the blisters have normally crusted over. The rash can appear on the face, scalp, body, or in and around the mouth, eyes and bottom. Other symptoms can include fever, headaches, chills, and muscle and/or joint aches and pains. Sometimes disease complications can occur such as bacterial infection of the skin (often due to scratching of the itchy rash/crusts), inflammation of the brain (varicella encephalitis), and lung infection (varicella pneumonia).

Full recovery from chickenpox generally occurs; however, later in life the virus can become active again. This condition is known as shingles or Herpes zoster.

Vaccination is the best way to protect against these severe diseases. The vaccine will not protect against diseases caused by other types of viruses or organisms.

Like other varicella vaccines, PRIORIX-TETRA cannot completely protect your child against catching chickenpox. However, people who have been vaccinated and catch chickenpox usually have a very mild disease, compared with people who have not been vaccinated.

Although PRIORIX-TETRA contains live viruses, they are too weak to cause severe disease in healthy people. Occasionally, some spots, blisters and fever may appear in the first two weeks after vaccination.

BEFORE RECEIVING PRIORIX-TETRA

DO NOT HAVE PRIORIX-TETRA IF:

  • your child has had an allergic reaction to PRIORIX-TETRA, or any ingredient contained in this vaccine. The ingredients are listed at the end of this leaflet. Signs of an allergic reaction may include itchy skin, rash, shortness of breath and swelling of the face or tongue.
  • your child is known to be allergic to neomycin. Signs of an allergic reaction are listed above. If your child has a history of skin allergy to neomycin they can still be vaccinated.

If your child has had PRIORIX-TETRA or another vaccine containing measles, mumps, rubella or varicella before and became unwell, tell your doctor or nurse before the next dose is given.

  • your child has a severe infection with a high temperature. A minor infection such as a cold should not be a problem, but talk to your doctor or nurse about this before being vaccinated.
  • your child has ever had a severe allergic reaction to eggs or anything that contained eggs.
  • you are or think you may be pregnant or if you intend to become pregnant within one month. Your doctor will discuss with you the risks of receiving PRIORIX-TETRA prior to or during pregnancy.
  • your child has lowered immunity. This can occur in persons:
    - with inherited (or family history of) immune deficiency conditions
    - with abnormal blood conditions or blood protein (immunoglobulin) disorders
    - with cancer
    - receiving or who have received certain drugs (ie cyclosporin, corticosteroids, and cancer medicines)
    - receiving or who have received radiation therapy
  • the expiry date printed on the pack has passed
  • the packaging is torn or shows signs of tampering

If you are not sure whether PRIORIX-TETRA should be given, talk to your doctor or nurse. Do not give this vaccine to anyone else; your doctor has prescribed it specifically for you/or your child.

BEFORE HAVING PRIORIX-TETRA TELL YOUR DOCTOR IF

  • your child has any medical problems such as:
    - a history or family history of convulsions (fits or seizures)
    - a history or family history of allergic diseases
    - a skin allergy to neomycin
    - a bleeding disorder.
    Sometimes PRIORIX-TETRA may need to be given differently in people with bleeding problems.
    - a weakened immune system. Your child should be closely monitored as the response to the vaccine may not be sufficient to ensure protection against the illness.
  • your child has allergies to any other medicines or substances, such as dyes, foods or preservatives.
  • you are breast feeding. Your doctor will discuss the risks and benefits of vaccination.
  • your child has received another vaccine within the last month.
  • your child has received a blood or plasma transfusion, or been given gamma globulin or other immunoglobulin within the last 3 months. PRIORIX-TETRA may be less effective if given within 3 months of these products. Your doctor will decide when to give the vaccine.
  • your child is taking any prescription or OTC (over-the-counter) medicines. Some vaccines may be affected by other vaccines or medicines. Your doctor, nurse or pharmacist will be able to tell you what to do if PRIORIX-TETRA is to be given with another vaccine or medicine.
  • Your child has had any testing for tuberculosis (TB). PRIORIX-TETRA may affect the result of the tuberculin test.

Fainting can occur following, or even before, any needle injection, therefore tell the doctor or nurse if you/your child fainted with a previous injection.

HOW PRIORIX-TETRA IS GIVEN

The doctor or nurse will give PRIORIX-TETRA as an injection.

If you have any concerns about how this vaccine is to be given, talk to your doctor, nurse or pharmacist.

HOW MUCH IS GIVEN

PRIORIX-TETRA is generally given as a single 0.5mL dose.

HOW IT IS GIVEN

The vaccine comes as a powder which is mixed with sterile water before use. PRIORIX-TETRA is injected under the skin (subcutaneously) or into the muscle (intramuscularly). PRIORIX-TETRA is generally injected into the upper leg in infants under 12 months of age. In children over 12 months of age the injection may be given in the upper arm.

PRIORIX-TETRA should never be given into a vein.

WHEN IT WILL BE GIVEN

The appropriate time and number of doses that will be given will be determined by your doctor on the basis of appropriate official recommendations.

IF A DOSE IS MISSED

If your child misses a scheduled dose, talk to your doctor or nurse and arrange another visit as soon as possible.

AFTER RECEIVING PRIORIX-TETRA

THINGS YOU MUST NOT DO:

  • do not become pregnant for one month after receiving PRIORIX-TETRA vaccination. Talk to your doctor as soon as possible, if you do become pregnant within this time.

THINGS YOU MUST DO:

Tell your doctor your child has received PRIORIX-TETRA if:

  • they are to have a tuberculin skin test for tuberculosis within 4-6 weeks after vaccination. The results of the test may be affected by the vaccine.
  • they are to have another vaccine within 1 month after vaccination.
  • they are to have a blood or plasma transfusion, or be given gamma globulin or other immunoglobulin within 2 weeks after vaccination.

THINGS TO BE CAREFUL OF:

It is advised to remain in the clinic for about 15 minutes after receiving the injection. There is a rare risk of allergic reactions. These may be local or widespread rashes that may be itchy or blistering, swelling of the eyes and face, difficulty in breathing or swallowing, a sudden drop in blood pressure and loss of consciousness. These reactions will usually occur before leaving the doctor’s surgery. If these symptoms occur, you should contact a doctor immediately.

SIDE EFFECTS

Tell your doctor, nurse or pharmacist as soon as possible if you (or your child) have troublesome symptoms after having had a dose of PRIORIX-TETRA.

PRIORIX-TETRA helps protect most people from measles, mumps, rubella and varicella infection, but it may have unwanted side effects in a few people. All medicines and vaccines can have side effects. Sometimes they are serious; most of the time they are not. Some side effects may need medical treatment. The chance of your child having a serious side effect is very much less than the chance of you or your child having a permanent injury from the natural infections.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Most unwanted effects with PRIORIX-TETRA are mild. These effects, as with other vaccines, generally occur around the injection site.

Side effects that occurred during clinical trials with PRIORIX-TETRA were as follows:

Very common (these may occur with more than 1 in 10 doses of the vaccine):

  • pain and redness around the injection site
  • fever greater than 37.5°C*

Common (these may occur with up to 1 in 10 doses of the vaccine):

  • swelling around the injection site
  • fever greater than 39°C*
  • irritability
  • rash (spots and/or blisters)

* Higher rates of fever were observed after administration of the first dose of PRIORIX-TETRA when compared to measles-mumps-rubella and varicella vaccines administered separately at the same visit.

Uncommon (these may occur with up to 1 in 100 doses of the vaccine):

  • crying
  • generally feeling unwell
  • loss of appetite
  • vomiting
  • diarrhoea
  • nervousness
  • inability to sleep
  • sleepiness
  • tiredness (fatigue)
  • lack of energy
  • runny nose
  • upper respiratory tract infection
  • swollen glands in the cheek
  • swollen glands in the neck, armpit and groin

Rare (these may occur with up to 1 in 1,000 doses of the vaccine):

  • seizures with fever
  • coughing
  • infection of the middle ear
  • bronchitis

After commercialisation, the following additional side effects have been rarely reported in people vaccinated with PRIORIX-TETRA:

  • chickenpox-like rash
  • shingles (herpes zoster)
  • mumps like symptoms (including transient, painful swelling of the testicles and swollen glands in the neck)
  • temporary lumpy rash that may affect the skin, mouth and other parts of the body
  • joint and muscle pains
  • infection around the brain or spinal cord (meningitis)
  • infection or inflammation of the nervous system resulting in temporary loss of control of bodily movements, walking or sensation changes
  • bleeding or bruising more easily than normal which may be associated with skin rashes/peeling or fever

Other side effects not listed above, can also occur during or soon after a dose of PRIORIX-TETRA.

Check with your doctor or nurse if you or your child has any other effects.

Do not be alarmed by this list of possible side effects. You or your child may not experience any of them.

STORAGE

PRIORIX-TETRA is usually stored at the doctor’s clinic or surgery, or at the pharmacy. But if you need to store PRIORIX-TETRA always:

  • Keep PRIORIX-TETRA in the refrigerator stored between 2°C and 8°C. DO NOT STORE PRIORIX-TETRA IN THE FREEZER. Do not store it in the bathroom, near the sink, or leave it in the car on hot days. Avoid exposing the vaccine to sunlight.
  • Keep the vaccine out of the reach of children.
  • Keep PRIORIX-TETRA in the original pack until it is time for it to be given.

Ask your pharmacist what to do with any left over PRIORIX-TETRA that has expired or has not been used.

PRODUCT DESCRIPTION

WHAT IT LOOKS LIKE

PRIORIX-TETRA comes as a whitish to slightly pink powder in a glass vial. This is mixed (reconstituted) with water diluent supplied in a glass ampoule or syringe. The reconstituted vaccine may vary in colour from clear peach to fuchsia pink.

The vaccine should be injected as soon as possible after reconstitution, and no later than 8 hours after reconstitution.

INGREDIENTS

The active ingredients of PRIORIX-TETRA are live weakened measles, mumps, rubella and varicella viruses in a dry powder. Each 0.5mL dose contains not less than:

  • 103.0 CCID50 (cell culture infectious dose 50%) of the Schwarz measles
  • 104.4 CCID50 of the RIT 4385 mumps,
  • 103.0 CCID50 of the Wistar RA 27/3 rubella and
  • 103.3 PFU (plaque forming units) of the OKA varicella-zoster virus strains.

The inactive ingredients in the vaccine are: lactose monohydrate, amino acids, sorbitol and mannitol. Neomycin sulphate is present as a residual from the manufacturing process. The vaccine is mixed with sterile Water for Injections before use.

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.

FURTHER INFORMATION

PRIORIX-TETRA is only available if prescribed by a doctor.

PRIORIX-TETRA comes as a whitish to slightly pink powder in a glass vial as:

  • individual packs containing one vial of vaccine and one ampoule of sterile water diluent (AUST R 107285)
  • packs of 10 vials of vaccine (AUST R 107284) and separate packs of 10 ampoules of sterile water diluent (AUST R 13051)
  • packs of 10 vials of vaccine and 10 ampoules of sterile water diluent (AUST R 107285)
  • individual packs containing one vial of vaccine and one syringe of sterile water diluent (AUST R 107286)
  • packs of 10 vials of vaccine and 10 syringes of diluent (AUST R 107286)

MANUFACTURER

GlaxoSmithKline Biologicals s.a.
Rue de l'Institut 89,
1330 Rixensart, Belgium.

DISTRIBUTED IN AUSTRALIA BY

GlaxoSmithKline Australia Pty Ltd
Level 4, 436 Johnston Street
Abbotsford, Victoria 3067, Australia

Date of Preparation:

18 July 2017

Version 5.0

Trade marks are owned by or licensed to the GSK group of companies.

©2017 GSK group of companies or its licensor.

BRAND INFORMATION

Brand name

Priorix-Tetra Powder for injection

Active ingredient

Varicella zoster vaccine, live attenuated; Rubella vaccine, live; Mumps vaccine, live; Measles vaccine, live

Schedule

S4

 

1 Name of Medicine

Measles virus, mumps virus, rubella virus and live varicella vaccine.

6.7 Physicochemical Properties

Not relevant to vaccines.

2 Qualitative and Quantitative Composition

Priorix-Tetra is a sterile lyophilised mixed preparation containing the attenuated Schwarz measles virus strain, the RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain), the Wistar RA 27/3 rubella virus strain and the OKA strain of varicella zoster virus. Each virus strain is separately produced in either chick embryo cells (mumps and measles) or MRC5 human diploid cells (rubella and varicella).
Each 0.5 mL dose of the reconstituted vaccine contains not less than 103.0 CCID50 (cell culture infective dose 50%) of the Schwarz measles, not less than 104.4 CCID50 of the RIT 4385 mumps, not less than 103.0 CCID50 of the Wistar RA 27/3 rubella and not less than 103.3 plaque forming units (PFU) of the varicella zoster OKA virus strains. The four virus strains are mixed prior to lyophilisation.
The manufacture of this product includes exposure to bovine derived materials sourced to minimise the risk of prion contamination. 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.
Priorix-Tetra meets the World Health Organisation requirements for manufacture of biological substances and for measles, mumps, rubella and varicella vaccines and combined vaccines (live).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder and diluent for solution for injection.
Priorix-Tetra is presented as a whitish to slightly pink powder for reconstitution with clear and colourless sterile water for injection diluent. The colour of the reconstituted vaccine may vary from clear peach to fuchsia pink.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Priorix-Tetra induces protective antibodies against all four viruses.

Clinical trials.

Immunogenicity studies.

Immunogenicity data of Priorix-Tetra has not been studied in subjects above 6 years of age, but Priorix-Tetra may be used in subjects up to 12 years of age based on previous experience with the separate component vaccines, Priorix and Varilrix.

Priorix-Tetra administered in a 2 dose schedule.

The immunogenicity with the commercial formulation of Priorix-Tetra has been established in randomised controlled clinical trials comparing Priorix-Tetra with separate injections of measles, mumps and rubella (Priorix) and varicella (Varilrix) vaccines in subjects aged 11 to 23 months. Approximately 2,000 subjects randomised to receive two subcutaneous doses of Priorix-Tetra given six weeks apart, were compared to approximately 500 subjects randomised to receive two doses of Priorix six weeks apart and one dose of Varilrix at the time of first vaccination. Seroconversion data were collected 42 days following each vaccination. See Table 3.
Three years after vaccination with two doses of Priorix-Tetra, 98.5%, 97.4%, 100% and 99.4% of all vaccinees were still seropositive for respectively antimeasles, antimumps, antirubella and antivaricella antibodies.
In a study with an earlier formulation of the GSK MMRV combination vaccine (with a reduced mumps content) a total of 300 healthy infants aged 9 to 10 months, without previous history of varicella were administered either 2 doses of GSK MMRV combination vaccine or 2 doses of Priorix and Varilrix. Doses were administered with an interval of 3 months. All subjects were seropositive for all four vaccine antigens after two doses of this predecessor formulation of Priorix-Tetra. After a first dose seroconversion rates were comparable for all antigens to those seen in 12-24 months old children in other clinical studies except as expected mumps and a lower trend for measles. After the second dose of these respective vaccines all subjects had seroconverted, with antirubella GMTs similar in both groups and antimeasles, antimumps and antivaricella GMTs higher in the predecessor formulation of Priorix-Tetra group compared to Priorix + Varilrix.

Priorix-Tetra administered as second dose after a first dose of MMR/V.

Priorix-Tetra administered as a second dose of MMR vaccine in children 15 months to 6 years of age was evaluated in 2 clinical studies. Children were previously primed with respectively an MMR vaccine (N = 458) or with an MMR vaccine coadministered with a live attenuated varicella vaccine (N = 390) and randomised to receive either Priorix-Tetra or Priorix and Varilrix given concomitantly.
Seropositivity rates after administration of Priorix-Tetra for antivaricella antibodies were 97.9% (IFA) in children [between 15 months and 6 years of age] previously vaccinated with MMR and 100% in children previously vaccinated with an MMR vaccine coadministered with a live attenuated varicella vaccine. Seropositivity rates were at least 99.5% for antimeasles, mumps and rubella antibodies in both studies. Immune responses in terms of GMTs for measles, mumps, rubella and varicella obtained with Priorix-Tetra were comparable with the immune responses obtained with Priorix and Varilrix administered as separate injections.

Efficacy studies.

In clinical studies it has been shown that the vast majority of subjects who receive varicella vaccines and are exposed to wild type virus are either completely protected from chickenpox or develop a milder form of the disease (breakthrough varicella).
The efficacy of GlaxoSmithKline (GSK)'s OKA/RIT varicella vaccines in preventing confirmed varicella disease (varicella cases were confirmed by polymerase chain reaction [PCR] or exposure to a varicella case) has been evaluated in a large active controlled clinical trial in which children aged 12-22 months received two doses of Priorix-Tetra (N = 2279), given six weeks apart, or one dose of Varilrix (N = 2263). The coprimary objective to demonstrate vaccine efficacy with Priorix-Tetra on a two dose schedule was met. The coprimary objective of this trial with respect to Varilrix was to demonstrate vaccine efficacy of ≥ 60% in comparison to Priorix. The efficacy of Varilrix (one dose) versus Priorix in respect of preventing confirmed varicella cases was 65.4% (97.5% CI: 57.2-72.1%), the lower limit of the 2 sided 97.5% CI however did not exceed the predefined criterion of 60%. The observed vaccine efficacy against confirmed varicella of any severity and against moderate or severe confirmed varicella after 2 doses of Priorix-Tetra and after one dose of Varilrix (mean follow up period 35 months) are presented in Table 4.
In a pivotal clinical study in subjects receiving two doses of Priorix-Tetra given six weeks apart, at the one year follow up after the second dose of Priorix-Tetra, no breakthrough cases were reported for measles, mumps and rubella despite reported contacts with wild virus. Exposures to varicella or zoster were reported in 14.5% in the Priorix-Tetra group versus 20.0% in the control group (Priorix + Varilrix for the first dose; Priorix alone for the second dose). Breakthrough cases were reported in 0.34% of Priorix-Tetra recipients, as opposed to 1.9% of children in the control group.
After 3 years follow up of the same study, lower incidences of varicella breakthrough cases were reported in the group receiving two doses of Priorix-Tetra (1 case, 0.44%) than in the group receiving only one dose of Varilrix (4 cases, 5.06%), however the number of breakthrough cases were too small to make any conclusion about comparative vaccine efficacy. No cases of measles, mumps or rubella breakthrough disease were reported in any group during this 3 years follow up.
In a study specifically designed to evaluate vaccine efficacy with Varilrix, which contains the same active ingredient as Priorix-Tetra, 493 children aged 10 to 30 months old were followed up for a period of 29.3 months. The protective efficacy was 100% against common clinical cases of varicella and 88% against any cases.
The immunogenicity and safety of Priorix-Tetra administered intramuscularly was evaluated in one comparative study conducted in 328 children who received Priorix-Tetra either by intramuscular or subcutaneous route. The study demonstrated similar immunogenicity and safety profiles for both administration routes.

Effectiveness studies.

Effectiveness data from an outbreak investigation suggest a higher level of protection and a decrease in breakthrough varicella (not statistically significant) following two doses of varicella containing vaccine than following one dose. The effectiveness of two doses of Priorix-Tetra was 91% (95% CI: 65-98%) against any disease and 94% (95% CI: 54-99%) against moderate disease.

5.2 Pharmacokinetic Properties

Not relevant to vaccines.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

Priorix-Tetra has not been evaluated for carcinogenicity or mutagenicity.

4 Clinical Particulars

4.1 Therapeutic Indications

Priorix-Tetra is indicated for active immunisation against measles, mumps, rubella and varicella from 9 months of age.

4.3 Contraindications

Priorix-Tetra is contraindicated in pregnant women. If vaccination of postpubertal women occurs, pregnancy should be avoided for one month (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Priorix-Tetra is contraindicated in children and adults with known hypersensitivity to neomycin or to any other component of the vaccine (for egg allergy, see Section 4.4 Special Warnings and Precautions for Use). A history of contact dermatitis to neomycin is not a contraindication.
Priorix-Tetra is contraindicated in children and adults having shown signs of hypersensitivity after previous administration of measles, mumps, rubella and/or varicella vaccines.
Priorix-Tetra is contraindicated in patients with severe humoral or cellular (primary or acquired) immunodeficiency e.g. those receiving high dose steroids (further guidance is found in the Australian Immunisation Handbook) (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

As with other vaccines, the administration of Priorix-Tetra should be postponed in children and adults suffering from acute severe febrile illness (T > 38.5°C). However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination.
Priorix-Tetra must not be administered intravascularly or intradermally.
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. It is important that procedures are in place to avoid injury from faints.
As with all injectable vaccines, appropriate medical treatment (i.e. adrenaline) and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.
Alcohol and other disinfecting agents, if used, must be allowed to evaporate from the skin before injection of the vaccine as they can inactivate the attenuated viruses in the vaccine.
Limited protection against measles or varicella may be obtained by vaccination up to 72 hours after exposure to natural disease.
Infants in their first year of life may not respond sufficiently to the measles component of the vaccine due to the possible persistence of maternal measles antibodies. Additional doses of a measles containing vaccine should be given according to official recommendations.
The antibody response to the rubella and mumps components is too slow for effective postexposure prophylaxis.
Transmission of measles, mumps and rubella viruses from vaccinees to susceptible contacts has never been documented, although pharyngeal excretion of the rubella vaccine virus is known to occur about 7 to 28 days after vaccination with peak excretion around the 11th day. Transmission of the Oka vaccine virus has been shown to occur at a very low rate in seronegative contacts of vaccinees with rash. Transmission of the Oka vaccine from a vaccinee who does not develop a rash to seronegative contacts cannot be excluded. Vaccine recipients should attempt to avoid contact for up to 6 weeks, where possible, with immunocompromised individuals who are susceptible to varicella.

Febrile convulsions.

There is an increased risk of fever and febrile convulsions 5 to 12 days after Priorix-Tetra when used as the first measles containing vaccination, as compared with 2 separate injections of MMR and varicella vaccines (see Section 4.8 Adverse Effects (Undesirable Effects)). There was no indication of an increased risk when used as the second measles containing vaccination.
Fever rates are usually high after the first dose of measles containing vaccines. Vaccination of children and adults with a history of febrile convulsions or a family history of convulsions should be considered with caution. Alternative immunisation of these children and adults with separate MMR and varicella vaccines should be considered for the first dose (see Section 4.2 Dose and Method of Administration). In any case vaccinees should be monitored for fever during the risk period ranging from 5 to 12 days after vaccination.
The measles and mumps components of the vaccine are produced in chick embryo cell culture and may therefore contain traces of egg protein. Vaccination of persons with a history of anaphylactic, anaphylactoid, or other immediate reactions (e.g. generalised urticaria, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) subsequent to egg ingestion cannot be recommended and should only be considered after careful assessment of the benefits and potential risks of administering Priorix-Tetra on an individual basis. Individuals who have experienced anaphylaxis after egg ingestion should be vaccinated with extreme caution, with adequate treatment for anaphylaxis on hand.
Egg allergies other than anaphylactic or anaphylactoid reactions are not considered to constitute an increased risk. Children and adults who have experienced such reactions may be considered for vaccination. There is no evidence to indicate that persons with allergies to chickens or feathers are at increased risk of reaction to the vaccine.
As for any vaccine, immunisation with measles, mumps, rubella and varicella vaccine may not result in seroconversion in 100% of susceptible persons given the vaccine. As for other varicella vaccines, cases of varicella disease have been shown to occur in persons who have previously received Priorix-Tetra. These breakthrough cases are usually mild, with a fewer number of lesions and less fever as compared to cases in unvaccinated individuals.
Cases of worsening of thrombocytopenia and recurrence of thrombocytopenia in children who suffered thrombocytopenia after the first dose have been reported following vaccination with live measles, mumps and rubella vaccines. In such cases, the risk-benefit of immunising with Priorix-Tetra should be carefully evaluated.
There is limited data on the use of Priorix-Tetra in immunocompromised patients, therefore vaccination should be considered with caution and only when, in the opinion of the physician, the benefits outweigh the risks, further guidance is found in the Australian Immunisation Handbook.
Immunocompromised patients who have no contraindication for this vaccination (see Section 4.3 Contraindications) may not respond as well as immunocompetent patients, therefore some of these patients may acquire measles, mumps, rubella or varicella despite appropriate vaccine administration. Immunocompromised patients should be monitored carefully for signs of measles, mumps, rubella and varicella.
Very few reports exist on disseminated varicella with internal organ involvement following vaccination with the Oka varicella vaccine strain and these are mainly in immunocompromised patients.
No clinical data are available on the safety, immunogenicity, and efficacy of Priorix-Tetra in adolescents and adults.

Use in the elderly.

No data available.

Paediatric use.

See Section 4.4 Special Warnings and Precautions for Use.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Clinical studies have demonstrated that Priorix-Tetra can be given simultaneously with any of the following monovalent or combination vaccines: hexavalent vaccines (DTPa-HBV-IPV/Hib), diphtheria-tetanus-acellular pertussis vaccine (DTPa), Haemophilus influenzae type b vaccine (Hib), inactivated polio vaccine (IPV), hepatitis B vaccine (HBV), hepatitis A vaccine (HAV), meningococcal serogroup B vaccine (MenB), meningococcal serogroup C conjugate vaccine (MenC), meningococcal serogroups A, C, W-135 and Y conjugate vaccine (MenACWY) and 10-valent pneumococcal conjugate vaccine (PCV).
If Priorix-Tetra is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.
Data are not available on the concurrent administration of Priorix-Tetra with Men CCV or the PRP-OMP type Hib vaccine which are included in the ASVS at 12 months of age.
If Priorix-Tetra cannot be given at the same time as another live attenuated vaccine, an interval of at least 1 month should be left between the two vaccinations.
If tuberculin (Mantoux) testing is needed, it should be carried out before, or simultaneously with vaccination since it has been reported that combined measles, mumps and rubella vaccines may cause a temporary depression of tuberculin skin sensitivity. As this allergy may last up to a maximum of 6 weeks, tuberculin testing should not be performed within that period after vaccination to avoid false negative results.
In children and adults who have received human gammaglobulins or a blood transfusion, vaccination should be delayed for at least 3 months because of the possibility of vaccine failure due to passively acquired antibodies.
Salicylates should be avoided for 6 weeks after each vaccination as Reye's syndrome has been reported following the use of salicylates during natural varicella infection.
Priorix-Tetra should not be mixed with other vaccines in the same syringe.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Priorix-Tetra has not been evaluated for its potential to impair fertility.
(Category B2)
Pregnant women must not be vaccinated with Priorix-Tetra. Pregnancy should be avoided for one month after vaccination. Women who intend to become pregnant should be advised to delay pregnancy (see Section 4.3 Contraindications).
Adequate human data on the use of Priorix-Tetra during pregnancy are not available and animal studies on reproductive toxicity have not been conducted.
Women of childbearing age should be tested for rubella antibodies prior to pregnancy. All seronegative women, provided they are not pregnant, should be offered rubella vaccine. Those administering the vaccine should be careful to instruct women to whom it is given that they should not become pregnant for at least one month after vaccination because rubella vaccine can cause foetal infection. The rubella vaccine cannot be considered teratogenic during pregnancy and need not be the reason to recommend termination of pregnancy. The final decision must be made by the patient and her physician.
There is little human data regarding use in breastfeeding women. Persons can be vaccinated where the benefit outweighs the risk.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial experience.

Adverse events which might occur following the use of a combined mumps, measles, rubella and varicella vaccine correspond to those observed after administration of the monovalent vaccines alone or in combination.

Priorix-Tetra administered in a 2 dose schedule.

In controlled clinical studies, signs and symptoms were actively monitored after administration of the commercial formulation of Priorix-Tetra to 2,206 subjects. The following table (Table 1) displays a pooled analysis of the incidence of solicited symptoms reported during the 4 day follow up after vaccination for pain, redness and swelling, the 15 day follow up for fever and the 43 day follow up for rash, after each vaccination dose. It compares Priorix-Tetra given in a 2 dose schedule in healthy children in the second year of life, with separate administration of Priorix and Varilrix.
Analysis of the three pivotal studies has shown that redness was the most frequently reported solicited local symptom, in both vaccine treatments. There was no difference between the vaccination regimens, after the first dose.
After the second dose, redness was significantly more frequent in the children who received Priorix-Tetra with respect to those who received Priorix. No differences in the incidences of pain or swelling between groups were seen after the first dose, however, like redness, both were seen significantly more frequently in children given Priorix-Tetra vaccine, after the second dose.
The observed incidence of fever during the first 15 day follow up period was higher in the pooled Priorix-Tetra group as compared to the Priorix and Varilrix group. Differences between groups were statistically significant for fever of any intensity (≥ 38.0°C) and for grade 3 fever (> 39.5°C). After the second dose, no differences in fever symptoms were observed in between the two vaccine groups. The use of antipyretics might be considered after vaccination.
For rash, no statistically significant differences were observed between vaccine groups for either the first or the second dose.

Other events.

Other unsolicited events reported in clinical trials for Priorix-Tetra are listed below. Causality has not formally been established. The safety profile presented below is based on data from more than 6,700 doses administered subcutaneously to children from 9 to 27 months of age. Events were recorded for up to 42 days after vaccination.
Very common events: ≥ 1/10. Common events: ≥ 1/100 and < 1/10. Uncommon events: ≥ 1/1,000 and < 1/100. Rare events: ≥ 1/10,000 and < 1/1,000. Very rare events: < 1/10,000.

Infections and infestations.

Uncommon: upper respiratory tract infection. Rare: otitis media.

Blood and lymphatic system disorders.

Uncommon: lymphadenopathy.

Metabolism and nutrition disorders.

Uncommon: anorexia.

Psychiatric disorders.

Common: irritability.
Uncommon: abnormal crying, nervousness, insomnia, somnolence.

Nervous system disorders.

Rare: febrile convulsions.

Respiratory, thoracic and mediastinal disorders.

Uncommon: rhinitis. Rare: cough, bronchitis.

Gastrointestinal disorders.

Uncommon: parotid gland enlargement, diarrhoea, vomiting.

Skin and subcutaneous tissue disorders.

Common: rash.

General disorders and administration site conditions.

Very common: pain and redness at the injection site, fever (rectal ≥ 38°C - ≤ 39.5°C, axillary/oral: ≥ 37.5°C - ≤ 39°C).
Common: swelling at the injection site, fever (rectal > 39.5°C, axillary/ oral > 39°C). Uncommon: lethargy, malaise, fatigue.

Priorix-Tetra administered as second dose after a first dose of MMR/V.

Priorix-Tetra administered as a second dose of MMR vaccine in children 15 months to 6 years of age was evaluated in 2 clinical studies. Children were previously primed with respectively an MMR vaccine (MMR; N = 478) or with an MMR vaccine coadministered with a live attenuated varicella vaccine (MMR + V; N = 390) and randomised in both studies to receive either Priorix-Tetra or Priorix and Varilrix given concomitantly.
In both studies, the incidence of local solicited symptoms (pain, redness and swelling) was reported during the 4 day follow up after vaccination with Priorix-Tetra or Priorix and Varilrix. There was no difference between the vaccination regimens with regards to pain, redness and swelling in the study where children were primed with an MMR vaccine only. In the study where children were primed with an MMR vaccine coadministered with a varicella vaccine exploratory analyses showed a statistically significantly higher incidence of pain with Priorix-Tetra (33.3% vs 23.7%; p = 0043). The other notable effect, although not statistically significant in the exploratory analysis, is the difference in redness grade 3 (> 20 mm) which was 14.4% in the Priorix-Tetra group as compared to 8.2% in the group receiving Priorix and Varilrix (p = 0.077).
In both studies, the incidence of fever was reported during the 15 day and 43 day follow up period after vaccination with Priorix-Tetra or Priorix and Varilrix. Rash was reported during the 43 day follow up period. An exploratory analysis showed no statistical differences between the vaccination regimens with respect to all fever or grade 3 fever (> 39.5°C). Similar incidences of rash were obtained in both groups.
The reported incidence of local solicited symptoms, fever and rash following Priorix-Tetra or Priorix and Varilrix administered to children who had previously received a single dose of MMR is provided in Table 2.
When summarised according to age stratum for toddlers (15 months-2 years) and children (2-6 years) lower levels of all fever were reported in toddlers who received Priorix-Tetra as a second dose of a measles containing vaccine post-MMR vaccine (40.9%), compared to studies where toddlers were administered Priorix-Tetra as a first dose of a measles containing vaccine (61.15%). Fever > 39.5°C was observed in 2.7% of toddlers who received Priorix-Tetra as a second dose of a measles containing vaccine post-MMR vaccine, compared with 11.2% in studies where Priorix-Tetra was used as the first dose of a measles containing vaccine.

Post-marketing data.

During post-marketing surveillance, the following reactions have been reported additionally in temporal association with measles, mumps, rubella and varicella vaccination.

Infections and infestations.

Rare: meningitis, herpes zoster, measles-like syndrome, mumps-like syndrome (including orchitis, epididymitis and parotitis).

Blood and lymphatic system disorders.

Rare: thrombocytopenia, thrombocytopenic purpura.

Immune system disorders.

Rare: allergic reactions (including anaphylactic and anaphylactoid reactions).

Nervous system disorders.

Rare: encephalitis, cerebrovascular accident, cerebellitis, cerebellitis-like symptoms (including transient gait disturbance and transient ataxia), Guillain-Barré syndrome, transverse myelitis, peripheral neuritis.

Vascular disorders.

Rare: vasculitis (including Henoch-Schonlein purpura and Kawasaki syndrome).

Skin and subcutaneous tissue disorders.

Rare: erythema multiforme, varicella-like rash.

Musculoskeletal and connective tissue disorders.

Rare: arthralgia, arthritis.

Febrile convulsions.

The risk of febrile convulsions in children aged 9 to 30 months following Priorix-Tetra given as the first measles containing vaccine compared with a matched cohort who received either MMR or concomitant MMR and varicella vaccination was assessed in a retrospective database analysis.
The study included 82,656 children immunized with Priorix-Tetra, 149,259 with MMR and 39,203 with separate MMR and varicella vaccines. The attributable risk of febrile convulsions in the main risk period of 5 to 12 days following Priorix-Tetra was 3.64/10,000 (95% CI: -6.11; 8.30), corresponding to 1 additional case of febrile convulsions per 2,747 subjects receiving Priorix-Tetra as the first dose of measles containing vaccination compared to MMR or concomitant MMR and varicella vaccination.
In the 0 to 30 day time period following vaccination the attributable risk was 3.88/10,000 (95% CI: -14.25;15.93), corresponding to 1 additional case of febrile convulsions per 2,577 subjects receiving Priorix-Tetra. When used as the second measles containing vaccination, there is no indication of an increased risk.

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.

4.2 Dose and Method of Administration

Dosage (dose and interval).

Infants and children aged from 9 months to 12 years should receive two doses of Priorix-Tetra. The dose interval should preferably be between 6 weeks to 3 months. As with other live viral vaccines, in no circumstances should this interval be less than 4 weeks.
Alternatively, and in accordance with applicable official recommendations:
a single dose of Priorix-Tetra may be administered to children who have already received a single dose of another measles, mumps and rubella (MMR) vaccine with or without a single dose of another varicella vaccine;
a single dose of Priorix-Tetra may be administered followed by a single dose of another measles, mumps and rubella (MMR) vaccine with or without a single dose of another varicella vaccine.
Further guidance regarding the use of vaccines is found in the Australian Immunisation Handbook.
There is currently no clinical data available for the use of Priorix-Tetra in adolescents or adults.

Method of administration.

Priorix-Tetra is administered by subcutaneous (SC) or intramuscular (IM) injection. The vaccine should never be administered intravascularly or intradermally.
The Australian Immunisation Handbook recommends that MMR vaccines should be administered into the anterolateral thigh of children under 12 months of age. The deltoid region is the site of vaccination in children 12 months of age and older.
The vaccine should be administered subcutaneously in children with bleeding disorders (e.g. thrombocytopenia or any coagulation disorder).

Reconstitution.

The reconstituted vaccine should be inspected visually for any foreign particulate matter and/or abnormal physical appearance prior to administration. In the event of either being observed, do not administer the vaccine.
The colour of the reconstituted vaccine may vary from clear peach to fuchsia pink due to minor variations of its pH. This is normal and does not impair the performance of the vaccine. In the event of another variation being observed, do not administer the vaccine.
The vaccine should be injected as soon as possible after reconstitution. The reconstituted vaccine can be stored between 2 and 8°C, for up to 8 hrs before use. Contains no antimicrobial agent. Product is for single use in one patient only.
Any unused product or waste material should be disposed of in accordance with local requirements.

Instructions for reconstitution of the vaccine with diluent presented in ampoules.

Priorix-Tetra is reconstituted by adding the entire contents of the supplied ampoule of diluent to the vial containing the powder. The mixture should be well shaken until the powder is completely dissolved in the diluent.
After reconstitution, the vaccine should be used promptly.
Withdraw the entire contents of the vial. Inject the entire contents of the syringe, using a new needle for administration.

Instructions for reconstitution of the vaccine with diluent presented in pre-filled syringe.

Priorix-Tetra must be reconstituted by adding the entire content of the pre-filled syringe of diluent to the vial containing the powder.
To attach a needle to the syringe, carefully read the instructions given with Figure 1. However, the syringe provided with Priorix-Tetra might be slightly different than the syringe illustrated.
Always hold the syringe by the barrel, not by the syringe plunger or the Luer Lock Adaptor (LLA), and maintain the needle in the axis of the syringe (as illustrated in Figure 1). Failure to do this may cause the LLA to become distorted and leak.
During assembly of the syringe, if the LLA comes off, a new vaccine dose (new syringe and vial) should be used.
1. Unscrew the syringe cap by twisting it anticlockwise (as illustrated in Figure 1).
2. Attach a needle to the syringe by gently connecting the needle hub into the LLA and rotate a quarter turn clockwise until you feel it lock (as illustrated in Figure 1).
3. Remove the needle protector, which may be stiff.
4. Add the diluent to the powder. The mixture should be well shaken until the powder is completely dissolved in the diluent.
After reconstitution, the vaccine should be used promptly.
5. Withdraw the entire contents of the vial.
A new needle should be used to administer the vaccine. Unscrew the needle from the syringe and attach an injection needle by repeating step 2 above.
Inject the entire contents of the syringe.

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.

4.9 Overdose

Insufficient data are available.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The lyophilised vaccine also contains lactose monohydrate, amino acids and sorbitol and mannitol as stabilisers. Neomycin sulphate is present as a residual from the manufacturing process. There is no human serum albumin in Priorix-Tetra.

6.2 Incompatibilities

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

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

The vaccine should be stored between 2°C and 8°C in a refrigerator. Store in the original packaging in order to protect from light.

6.5 Nature and Contents of Container

Priorix-Tetra is presented as a whitish to slightly pink powder in a glass vial. The sterile water diluent is clear and colourless and is presented in a glass prefilled syringe or ampoule. The colour of the reconstituted vaccine may vary from clear peach to fuchsia pink due to minor variations of its pH. This is normal and does not impair the performance of the vaccine. In the event of another variation being observed, discard the vaccine.
Priorix-Tetra is available is pack sizes of 1 or 10.
Not all pack sizes and container types may be distributed in Australia.
The vials and prefilled syringes are made of neutral glass type I, which conforms to European Pharmacopoeia Requirements.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes