Data Sheet
PRIORIX-TETRA™
Live attenuated measles, mumps, rubella and varicella vaccine
Presentation
PRIORIX-TETRA™ is a sterile lyophilised mixed preparation of the attenuated Schwarz measles, RIT 4385 mumps (derived from Jeryl Lynn strain), Wistar RA 27/3 rubella and OKA varicella strains of viruses, separately produced in chick embryo cells (mumps and measles) or human diploid MRC5 cells (rubella and varicella).
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).
Each 0.5 mL dose of the reconstituted vaccine contains not less than 103.0 CCID50 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 PFU of the varicella virus strains.
Clinical Particulars
Therapeutic indications
PRIORIX-TETRA™ is indicated for active immunisation in subjects from the age of 9 months up to 12 years of age inclusive against measles, mumps, rubella and varicella.
Posology and method of administration
Posology
Primary immunisation consists of one dose of vaccine.
If official recommendations call for additional doses of measles, mumps, rubella and/or varicella, Priorix-Tetra can be used for these doses.
It is preferable to respect an interval of at least 6 weeks between doses. In no circumstances should this interval be less than 4 weeks.
Method of administration
For subcutaneous injection, preferably into the outer aspect of upper arm.
Contraindications
Priorix-Tetra is contraindicated in subjects with known hypersensitivity to neomycin or to any other component of the vaccine (for egg allergy, see Special Warnings and Special Precautions).
A history of contact dermatitis to neomycin is not a contraindication.
Priorix-Tetra is contraindicated in subjects having shown signs of hypersensitivity after previous administration of measles, mumps, rubella and/or varicella vaccines.
It is contra-indicated to administer Priorix-Tetra to pregnant females. Furthermore, pregnancy should be avoided for three months after vaccination (see Pregnancy).
Priorix-Tetra should not be given to subjects with impaired immune function. These include patients with primary or secondary immunodeficiencies.
Special warnings and special precautions for use
As with other vaccines, the administration of Priorix-Tetra should be postponed in subjects suffering from acute severe febrile illness. However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination.
As with all injectable vaccines, appropriate medical treatment 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 must be allowed to evaporate from the skin before injection of the vaccine since they can inactivate the attenuated viruses in the vaccine.
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.
A history of febrile convulsions or a family history of convulsions do not constitute a contra-indication for the use of Priorix-Tetra. Vaccinees with a history of febrile convulsions should be closely followed up as vaccine related fever may occur during the period ranging from 4 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. 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 may be at an enhanced risk of immediate-type hypersensitivity reactions after vaccination, although these types of reactions have been shown to be very rare. Individuals who have experienced anaphylaxis after egg ingestion should be vaccinated with extreme caution, with adequate treatment for anaphylaxis on hand should such a reaction occur.
Transmission of measles, mumps and rubella viruses from vaccinees to susceptible contacts has never been documented, although pharyngeal excretion of the rubella virus is known to occur about 7 to 28 days after vaccination with peak excretion around the 11th day. Post-marketing experience suggests that transmission of varicella vaccine virus may occur very rarely between healthy vaccinees who develop a varicella-like rash and healthy susceptible contacts.
Priorix-Tetra should under no circumstances be administered intravascularly or intradermally. Accidental intravascular administration may give rise to severe reactions or even shock. Immediate measures depend on the severity of the reaction.
As with any vaccine, a protective immune response may not be elicited in all vaccinees.
The use of Priorix-Tetra in asymptomatic HIV subjects has not been studied. Administration of Priorix-Tetra may be considered with caution in this population when, in the opinion of the physician, withholding the vaccine entails a greater risk.
Interaction with other medicaments and other forms of interaction
Priorix-Tetra can be given simultaneously (but at separate injection sites) with any of the following monovalent or combination vaccines [including 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).
If tuberculin testing has to be done 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 anergy 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 subjects who have received human gammaglobulins or a blood transfusion, vaccination should be delayed for at least three months because of the likelihood 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.
Pregnancy and lactation
Pregnancy
It is contraindicated to administer Priorix-Tetra to pregnant women. Furthermore, pregnancy should be avoided for three months after vaccination. Adequate human data on the use of Priorix-Tetra during pregnancy are not available and animal studies on reproductive toxicity have not been conducted.
Lactation
Adequate human data on the use of Priorix-Tetra during lactation are not available.
Effects on ability to drive and use machines
Not applicable.
Undesirable effects
The safety profile presented below is based on data from more than 6,700 doses administered to children from 9 to 27 months of age. Events were recorded for up to 42 days after vaccination.
Frequencies per dose are defined as follows:
Very common: ≥ 10%
Common: ≥ 1% and < 10%
Uncommon: ≥ 0.1% and < 1%
Rare: ≥ 0.01% and < 0.1%
Very rare: < 0.01%
Infections and infestations:
Uncommon: upper respiratory tract infection
Rare: otitis media
Blood and lymphatic system disorders
Uncommon: lymphadenopathy
Endocrine disorders:
Uncommon: parotid swelling
Metabolism and nutrition disorders
Uncommon: anorexia
Psychiatric disorders:
Common: irritability
Uncommon: crying, nervousness, insomnia
Nervous system disorders:
Rare: febrile convulsions
Respiratory, thoracic and mediastinal disorders
Uncommon: rhinitis
Rare: cough, bronchitis
Gastrointestinal disorders:
Uncommon: 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
* Following the administration of the first dose of the combined measles-mumps-rubella-varicella vaccine, higher incidences of fever (approximately 1.5 fold) were observed when compared to the concomittant administration of measles-mumps-rubella and varicella vaccines at separate injection sites.
During post-marketing surveillance, the following additional reactions have been reported in temporal association with measles-mumps-rubella and varicella vaccination:
Infections and infestations: Meningitis
Blood and lymphatic system disorders: Thrombocytopenia, thrombocytopenic purpura
Immune system disorders: Allergic reactions (including anaphylactic and anaphylactoid reactions)
Nervous system disorders: Transverse myelitis, Guillain Barré syndrome, peripheral neuritis, encephalitis
Skin and subcutaneous tissue disorders: Erythema multiforme
Musculoskeletal and connective tissue disorders: Arthralgia, arthritis
General disorders and administration site conditions: Kawasaki syndrome
In rare cases a mumps-like condition with an abbreviated incubation period cannot be ruled out. In isolated cases transient, painful swelling of the testicles has been reported after combined mumps, measles, rubella vaccination.
Overdose
Insufficient data are available
Pharmacological Properties
Pharmacodynamic properties
Pharmaco-therapeutic group: Viral attenuated vaccine, ATC code J07BD54
Seroconversion rates elicited by two doses of Priorix-Tetra given with an interval of 6 weeks in approximately 2,000 previously unvaccinated children from 11 to 23 months of age are summarized in the table below:
| Antibody Test (cut-off) |
Post dose 1 | Post dose 2 |
|---|---|---|
| Measles ELISA (150mIU/ml) |
96.4% |
99.1% |
| Mumps ELISA (231U/ml) Neutralisations (1:28) |
91.3% 95.4% |
98.8% 99.4% |
| Rubella ELISA (4IU/ml) |
99.7% |
99.9% |
| Varicella IFA (1:4) |
97.2% |
99.8% |
In clinical trials, it has been shown that the vast majority of subjects who received varicella vaccines and are exposed to wild-type virus were either completely protected from chickenpox or developed a milder form of the disease (breakthrough varicella). Data suggest a higher efficacy and a decrease in breakthrough varicella following two doses of vaccine with respect to one dose.
Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not required for vaccines.
Preclinical safety data
A repeated dose toxicity study in animals did not reveal any local or systemic toxicity of the vaccine.
Pharmaceutical Particulars
List of excipients
Lactose, amino acids, mannitol, sorbitol, neomycin sulphate (residual), and water for injections.
Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Shelf life
2 years.
After reconstitution: immediate use is recommended. However the stability at + 2°C to + 8°C has been demonstrated for 8 hours after reconstitution.
Special precautions for storage
Store at 2°C - 8°C (in a refrigerator)
Do not freeze.
Store in the original packaging in order to protect from light.
Nature and contents of container
PRIORIX-TETRA™ is presented as a cake with a slightly pink colour in a glass vial. The sterile diluent is clear and colourless and presented in a glass prefilled syringe or ampoule. Due to minor variation of its pH, the reconstituted vaccine may vary in colour from colourless to light pink without deterioration of the vaccine potency. This is normal and does not impair the performance of the vaccine. In the event of other variation being observed, discard the vaccine.
Vials/prefilled syringes are made of neutral glass type I, which conforms to European Pharmacopoeia Requirements.
Instructions for use, handling and disposal
The diluent should be inspected visually for any foreign particulate matter and/or abnormal physical appearance. In the event of either being observed, discard the diluent.
The vaccine is reconstituted by adding the entire contents of the supplied container of diluent to the vial containing the powder. After the addition of the diluent to the powder, the mixture should be well shaken until the powder is completely dissolved.
Medicine Classification
Prescription Medicine
Package Quantities
PRIORIX-TETRA™ vaccine: monodose glass vials and pre-filled syringe diluent in packs of 1 and 10 with two separate needles. Packs of 1 and 10 without needles.
PRIORIX-TETRA™ vaccine: monodose glass vials and diluent ampoules in packs of 1 and 10.
PRIORIX-TETRA™ vaccine: monodose glass vials in packs of 10.
Not all pack sizes may be marketed
Name and Address
GlaxoSmithKline NZ Limited
AMP Centre
Cnr Albert & Customs Street
Private Bag 106600
Downtown
Auckland
NEW ZEALAND
ph (09) 367 2900
fax (09) 367 2506
Date of Preparation
15 October 2008