Priorix-Tetra^TM 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 (see also “Warnings and Precautions”).

Posology

Subjects from the age of 9 months up to and including 12 years of age should should receive 2 doses of Priorix-Tetra^TM to ensure optimal protection against measles, mumps, rubella and varicella (see Pharmacodynamics). 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.

 

Alternatively, and in accordance with applicable official recommendations*:

-        A single dose of Priorix-Tetra^TM may be administered to children who have already received a single dose of another measles, mumps and rubella (MMR) vaccine and/or a single dose of another varicella vaccine.

-        A single dose of Priorix-Tetra^TM may be administered followed by a single dose of another measles, mumps and rubella (MMR) vaccine and/or a single dose of another varicella vaccine.

 

* Applicable official recommendations may vary regarding the interval between doses and the need for one or two doses of measles, mumps and rubella and of varicella-containing vaccines.

 

Efficacy has not been evaluated in subjects above 6 years of age.

 

Method of administration

The vaccine is to be injected subcutaneously (SC) or intramuscularly (IM).

The preferred injection site is the deltoid region of the upper arm.

The vaccine should be administered subcutaneously in subjects with bleeding disorders (e.g. thrombocytopenia or any coagulation disorder).

For information on instructions for preparation or reconstitution please refer to the “Instructions for Use/Handling” section.

Priorix-TetraTM is contraindicated in subjects with known hypersensitivity to neomycin or to any other component of the vaccine (for egg allergy, see Warnings and Precautions). A history of contact dermatitis to neomycin is not a contraindication. Priorix-TetraTM is contraindicated in subjects having shown signs of hypersensitivity after previous administration of measles, mumps, rubella and/or varicella vaccines. Priorix-TetraTM is contra-indicated in pregnant women. Pregnancy should be avoided for one month after vaccination (see Pregnancy and Lactation). Priorix-TetraTM is contraindicated in subjects with severe humoral or cellular (primary or acquired) immunodeficiency (see also “Warnings and Precautions”).

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.

As with other vaccines, the administration of Priorix-Tetra^TM 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.

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.

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.

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.

There is an increased risk of fever and febrile convulsions 5 to 12 days after the first dose of Priorix-Tetra^TM as compared with 2 separate injections of MMR and varicella vaccines (see Adverse Reactions and Pharmacodynamics). There was no indication of an increased risk after the second dose.

Fever rates are usually high after the first dose of measles-containing vaccines.

Vaccination of subjects with a history of febrile convulsions or a family history of convulsions should be considered with caution. Alternative immunisation of these subjects with separate MMR and varicella vaccines should be considered for the first dose (see Posology). In any case, vaccinees should be monitored for fever during the risk period.

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 11^th 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.

Priorix-Tetra^TM must not be administered intravascularly or intradermally.

As with any vaccine, a protective immune response may not be elicited in all vaccinees.

As for other varicella vaccines, cases of varicella disease have been shown to occur in persons who have previously received Priorix-Tetra^TM. 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 subjects 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^TM should be carefully evaluated.

There is limited data on the use of Priorix-Tetra^TM in immunocompromised subjects, therefore vaccination should be considered with caution and only when, in the opinion of the physician, the benefits outweigh the risks.

Immunocompromised subjects who have no contraindication for this vaccination (see "Contraindications") may not respond as well as immunocompetent subjects, therefore some of these subjects may acquire measles, mumps, rubella or varicella despite appropriate vaccine administration. Immunocompromised subjects 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 Oka varicella vaccine strain mainly in immunocompromised subjects.

 

Clinical studies have demonstrated that Priorix-Tetra^TM 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 pneumococcal conjugate vaccine (PCV).

If Priorix-Tetra^TM is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

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

Pregnant women must not be vaccinated with Priorix-Tetra^TM. Pregnancy should be avoided for one month after vaccination. Women who intend to become pregnant should be advised to delay pregnancy.

 

Adequate human data on the use of Priorix-Tetra^TM 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^TM during lactation are not available.

NA

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.

 

Frequencies are reported as:

Very common (³1/10) / Common (³1/100 to <1/10) / Uncommon (³1/1,000 to <1/100) / Rare (³1/10,000 to <1/1,000) / Very rare (<1/10,000)

System Organ Class	Frequency	Adverse reactions
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	crying, nervousness, insomnia
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 ³38°C - £39.5°C; axillary/oral: ³37.5°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 concomitant administration of measles-mumps-rubella and varicella vaccines at separate injection sites.

 

 

 

During post-marketing surveillance, the following additional reactions have been reported after measles-mumps-rubella and varicella vaccination:

System Organ Class	Frequency	Adverse reactions
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

 

To report any side effect(s):

Kingdom of Saudi Arabia

National Pharmacovigilance centre (NPC)

• Fax: +966-11-205-7662

·         • Call NPC at +966-11-2038222, Ext: 2317-2356-2353-2354-2334-2340

• Toll-free: 8002490000

•  E-mail: npc.drug@sfda.gov.sa

•  Website: www.sfda.gov.sa/npc

 

 

 

 

 

 

Insufficient data are available.

Efficacy and effectiveness

The efficacy of GlaxoSmithKline’s Oka/RIT varicella  vaccines in preventing confirmed varicella disease (by RPCR or exposure to varicella case) has been evaluated in a large active controlled clinical trial in which children aged 12-22 months received two doses of Priorix-TetraTM (N = 2,279)  or one dose of monovalent Oka/RIT vaccine (N = 2,263). was  . s The observed vaccine efficacy against confirmed varicella of any severity and against moderate or severe confirmed varicella were respectively 94.9% (97.5% CI: 92.4;96.6%) and 99.5% (97.5% CI: 97.5;99.9%) after 2 doses of Priorix-TetraTM and 65.4 % (97.5% CI: 57.2;72.1%) and 90.7% (97.5% CI: 85.9;93.9%) after one dose of monovalent Oka/RIT vaccine (mean follow-up period 35 months).Group	Timing	Efficacy against confirmed varicella of any severity	Efficacy against moderate or severe confirmed varicella
Priorix-Tetra (2 doses)   N = 2,489	Year 2	94.9% (97.5% CI: 92.4;96.6)	99.5% (97.5% CI: 97.5;99.9)
	Year 6(1)	95.0% (95% CI: 93.6;96.2)	99.0% (95% CI: 97.7;99.6)
Monovalent Oka vaccine (1 dose)   N = 2,487	Year 2	65.4 % (97.5% CI: 57.2;72.1)	90.7% (97.5% CI: 85.9;93.9)
	Year 6(1)	67.0% (95% CI: 61.8;71.4)	90.3% (95% CI: 86.9;92.8)

Effectiveness data suggest a higher level of protection and a decrease in breakthrough varicella following two doses of varicella-containing vaccine than following one dose.

In an outbreak situation the effectiveness of two doses of Priorix-Tetra^TM was 91% (95% CI: 65;98%) against any disease and 94% (95% CI: 54;99%) against moderate disease.

 

Immune response

Seroconversion rates after two subcutaneous doses of Priorix-Tetra^TM 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)                  ELISA (50mIU/ml)	97.2% 89.4%	99.8% 99.2%

ELISA: Enzyme Linked Immuno Sorbent Assay

IFA: Immunofluorescence Assay

 

In a large efficacy trial, two years after vaccination with two doses of Priorix-Tetra^TM, seropositivity rates for anti-varicella antibodies were 99.4% (ELISA) and 99.2% (IFA) and respectively 99.1%, 90.5% and 100% for anti-measles, mumps and rubella antibodies (ELISA).

 

In children 9 to 10 months of age vaccinated with 2 doses of Priorix-Tetra^TM, seroconversion rates after a first dose of Priorix-Tetra^TM were comparable for all antigens except measles to those seen in 12-24 months old children in other clinical studies.

 

When Priorix-Tetra^TM administered as a second dose of MMR vaccine in children 24 months to 6 years of age, previously primed with an MMR vaccine or with MMR co-administered with a live attenuated varicella vaccine, all children were found seropositive for anti-measles, mumps and rubella antibodies. Seropositivity rates for anti-varicella antibodies were respectively 98.1% (IFA) and 100% in the children previously vaccinated with MMR or with MMR co-administered with a live attenuated varicella vaccine.

 

 

 

The immunogenicity and safety of Priorix-Tetra^TM administered intramuscularly was evaluated in one comparative study conducted in 328 children who received Priorix-Tetra^TM either by intramuscular or subcutaneous route. The study demonstrated similar immunogenicity and safety profiles for both administration routes.

Timing	Antibody Test (cut-off)
	Measles ELISA (150 mIU/ml)	Mumps ELISA (231 U/ml)	Rubella ELISA (4 IU/ml)
Year 2	99.1%	90.5%	100%
Year 6	99.0%	90.5%	99.8%

Post-Marketing Observational Safety Surveillance Study

The risk of febrile convulsions following the first dose vaccination of children aged 9 to 30 months with Priorix-Tetra^TM compared with a matched cohort who received MMR or simultaneous, but separate MMR and varicella vaccination, was assessed in a retrospective database analysis.

The study included 82,656 children immunized with MMRV, 149,259 with MMR and 39,203 with separate MMR and varicella vaccines.

The attributable risk of febrile convulsions on cohorts matched for confounding factors in the main risk period of 5 to 12 days following first dose of Priorix-Tetra^TM was 3.64/10,000 (95% CI: -6.11; 8.30).

 

 

 

 

No data

A repeated dose toxicity study in animals did not reveal any local or systemic toxicity of the vaccine.

Excipients of the vaccine are: amino acids, lactose, mannitol, sorbitol.

Solvent is water for injections.

Neomycin sulphate is present as a residual from the manufacturing process.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

The expiry date of the vaccine is indicated on the label and packaging. After reconstitution: immediate use is recommended. However the stability at + 2°C to + 8°C has been demonstrated for 8 hours after reconstitution.

Store at 2°C – 8°C (in a refrigerator)

Do not freeze.

Store in the original packaging in order to protect from light.

Powder in a vial (Type I glass) with a stopper.

0.5 ml of solvent in an ampoule (Type I glass)

or

0.5 ml of solvent in a pre-filled syringe (Type I glass) with rubber stopper, with or without needles

The reconstituted vaccine should be inspected visually for any foreign particulate matter and/or abnormal physical appearance. In the event of either being observed, the vaccine should be discarded.

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 other variation being observed, discard the vaccine.

 

Instructions for reconstitution of the vaccine with solvent presented in ampoules

Priorix-Tetra^TM is reconstituted by adding the entire contents of the supplied ampoule of solvent to the vial containing the powder. After the addition of the solvent to the powder, the mixture should be well shaken until the powder is completely dissolved in the solvent.

After reconstitution, the vaccine should be used promptly.

 

A new needle should be used to administer the vaccine.

 

Withdraw the entire contents of the vial.

 

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

Priorix-Tetra^TM must be reconstituted by adding the entire content of the pre-filled syringe of solvent to the vial containing the powder.

To attach the needle to the syringe, refer to the below drawing. However, the syringe provided with Priorix-Tetra^TM might be slightly different than the syringe described in the drawing

1.   Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise.

2.   To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock. (see picture)

3.      Remove the needle protector, which on occasion can be a little stiff.

Add the solvent to the powder. After the addition of the solvent to the powder, the mixture should be well shaken until the powder is completely dissolved in the solvent.

After reconstitution, the vaccine should be used promptly.

A new needle should be used to administer the vaccine.

 

Withdraw the entire contents of the vial.

 

Any unused product or waste material should be disposed of in accordance with local requirements.

 

Not all presentations are available in every country.

Priorix-Tetra is a trade mark of the GSK group of companies.

ã2016 GSK group of companies