Live attenuated varicella-zoster (Oka strain) virus* 10^3.3 plaque forming units (PFU)

*propagated in MRC5 human diploid cells

Adolescents ( 13 years) and Adults

Two doses (each of 0.5 ml of reconstituted vaccine) should be given, with an interval between doses of approximately eight weeks (minimum interval of six weeks).

There are insufficient data to determine the long-term protective efficacy of the vaccine. However, there is currently no evidence that further doses are routinely required following completion of a two-dose regimen in healthy adolescents and adults (see section 5.1).

If Varilrix is to be administered to seronegative subjects before a period of planned or possible future immunosuppression (such as those awaiting organ transplantation and those in remission from malignant disease), the timing of the vaccinations should take into account the delay after the second dose before maximal protection might be expected (see also sections 4.3, 4.4 and 5.1).

Children 1-12 years

Varilrix is not indicated for routine use in children. However, under the circumstances described in section 4.1, a single dose of 0.5 ml of reconstituted vaccine should be given.

Varilrix should not be administered to children aged less than one year.

Elderly

There are no data on immune responses to Varilrix in the elderly.

Method of administration

Varilrix is for subcutaneous administration only. The upper arm (deltoid region) is the preferred site of injection.

Varilrix should not be administered intradermally.

Varilrix must under no circumstances be administered intravascularly.

There are no data on the immune responses when different varicella-zoster vaccines are used for the first and second doses. Therefore, it is recommended that the same vaccine should be used for both doses.

A second dose of Varilrix is contra-indicated in subjects who have had a hypersensitivity reaction following the first dose.

Varilrix is contra-indicated during pregnancy and breast-feeding (see also sections 4.4 and 4.6).

Varilrix must not be administered to subjects with primary or acquired immunodeficiency states, such as subjects with leukaemias, lymphomas, blood dyscrasias, clinically manifest HIV infection, or patients receiving immunosuppressive therapy (including high dose corticosteroids).

Varilrix contains a live attenuated varicella-zoster virus and administration is contra-indicated during pregnancy (see sections 4.3 and 4.6). Due to an unknown degree of risk to the mother and to the fetus, female candidates for vaccination must be advised to take adequate precautions to prevent pregnancy occurring between the two doses and for three months after the second dose.

Serological studies of efficacy and post-marketing experience indicate that the vaccine does not completely protect all individuals from naturally-acquired varicella and cannot be expected to provide maximal protection against infection with varicella-zoster virus until about six weeks after the second dose (see section 5.1).

Administration of Varilrix to subjects who are in the incubation period of the infection cannot be expected to protect against clinically manifest varicella or to modify the course of the disease.

The rash produced during naturally-acquired primary infection with varicella-zoster may be more severe in those with existing severe skin damage, including severe eczematous conditions. It is not known if there is an increased risk of vaccine-associated skin lesions in such persons, but this possibility should be taken into consideration before vaccination.

Transmission of the vaccine viral strain

Transmission of vaccine viral strain has been shown to occur from healthy vaccinees to healthy contacts, to pregnant contacts and to immunosuppressed contacts. However, transmission to any of these groups occurs rarely or very rarely and has not been confirmed to occur in the absence of vaccine-associated cutaneous lesions in the vaccinee (see section 4.8).

In healthy contacts of vaccinees, seroconversion has sometimes occurred in the absence of any clinical manifestations of infection. Clinically apparent infections due to transmission of the vaccine viral strain have been associated with few skin lesions and minimal systemic upset.

However, contact with the following groups must be avoided if the vaccinee develops a cutaneous rash thought likely to be vaccine-related (especially vesicular or papulovesicular) within four to six weeks of the first or second dose and until this rash has completely disappeared (see also sections 4.6 and 5.1).

- varicella-susceptible pregnant women and

- individuals at high risk of severe varicella, such as those with primary and acquired immunodeficiency states. These include individuals with leukaemias, lymphomas, blood dyscrasias, clinically manifest HIV infections, and patients who are receiving immunosuppressive therapy, including high dose corticosteroids.

In the absence of a rash in the vaccinee, the risk of transmission of the vaccine viral strain to contacts in the above groups appears to be extremely small. Nevertheless, vaccinees (e.g. healthcare workers) who are very likely to come into contact with persons in the above groups should preferably avoid any such contact during the period between vaccinations and for 4-6 weeks after the second dose. If this is not feasible, then vaccinees should be vigilant regarding the reporting of any skin rash during this period, and should take steps as above if a rash is discovered.

Healthy seronegative children may be vaccinated if they are close contacts of persons who are at high risk of severe varicella infection (see sections 4.1 and 4.2). In these circumstances, continued contact between the vaccinee and the person at risk may be unavoidable. Therefore, the risk of transmission of the attenuated vaccine viral strain from the vaccinee should be weighed against the potential for acquisition of wild-type varicella-zoster by the at-risk person.

Aspirin and systemic salicylates should not be given to children under the age of 16, except under medical supervision, because of the risk of Reye's syndrome. Reye's syndrome has been reported in children treated with aspirin during natural varicella infection. However, there is no evidence to suggest that vaccination with Varilrix should be contrainidicated for older age-groups who need to take aspirin.

In a study in which Varilrix was administered to toddlers at the same time as, but at a different site to, a combined measles, mumps and rubella vaccine, there was no evidence of significant immune interference between the live viral antigens.

Varicella-zoster virus may cause severe clinical disease in pregnant individuals and may adversely affect the fetus and/or result in perinatal varicella, depending on the gestational stage when the infection occurs. Because the possible effects of infection with the vaccine viral strain on the mother and on the fetus are unknown, Varilrix must not be administered to pregnant women.

Furthermore, female candidates for vaccination must be advised to take adequate precautions to avoid pregnancy occurring between the two vaccine doses and for three months following the second dose.

Lactation

Undesirable effects that occurred during the 4-6 week period after vaccination were monitored using symptom checklists. The adverse events listed below were reported in temporal relationship with vaccination.

Frequencies, based on a total of 1141 doses administered to adolescents and adults, are reported as follows:

Very common: ( 10%)

Common: ( 1% and < 10%)

Uncommon: ( 0.1% and < 1%)

In adolescents and adults, the incidence of adverse reactions was not higher after the second dose with respect to the first.

The adverse events listed below were reported with similar frequencies following vaccination of 2624 children.

Injection site reactions:

very common: pain, redness, swelling

uncommon: inflammation, mass

Body as a whole:

common: fatigue, fever

uncommon: chest pain, malaise, pain

Central and peripheral nervous system:

common: headache

uncommon: dizziness, migraine

Gastrointestinal system:

uncommon: gastroenteritis, nausea

Musculoskeletal system:

uncommon: arthralgia, back pain, myalgia

Psychiatric:

uncommon: somnolence

Respiratory system:

uncommon: coughing, pharyngitis, rhinitis

Skin and appendages:

common: papulovesicular rash

uncommon: pruritis

White cell and reticuloendothelial system:

uncommon: lymphadenopathy

Post-marketing surveillance

Transmission of the vaccine virus from healthy vaccinees to healthy contacts has been shown to occur very rarely.

The following adverse events have been reported following vaccination of children, adolescents and adults with a frequency of less than 0.01%.

Injection site reactions

pain, redness, swelling

Body as a whole

fever

urticaria

anaphylactoid reaction

Skin and appendages

papulovesicular rash

The Oka strain virus contained in Varilrix was initially obtained from a child with natural varicella; the virus was then attenuated through sequential passage in tissue culture.

Natural infection induces a cellular and humoral immune response to the varicella-zoster virus, which can be rapidly detected following infection. IgG, IgM and IgA directed against viral proteins usually appear at the same time that a cellular immune response can be demonstrated, making the relative contribution of humoral and cellular immunity to disease progression difficult to ascertain. Vaccination has been shown to induce both humoral and cell-mediated types of immunity.

In clinical trials, the immune response to vaccination was routinely measured using an immunofluorescence assay. Antibody titres of 1:4 (the detection level of the test) were considered as positive.

In clinical trials that enrolled 211 adolescents and 213adults, all vaccinees had detectable levels of antibodies in blood samples taken six weeks after the second vaccine dose. Virtually all (98.7%) of the 1637 children tested had detectable antibodies six weeks after immunisation with one dose of vaccine.

In a follow-up study over 2 years in 159 vaccinated adult health care workers, 2 out of 72 (3%) vaccinees reporting contacts with wild-type chickenpox experienced mild breakthrough disease. Approximately one-third of the vaccinees showed an increase in antibody titre over the follow-up period, indicative of contact with the virus, without clinical evidence of varicella infection.

Slightly pink-coloured pellet in 3 ml vials (Type I glass) with stopper (bromobutyl rubber) and flip-off cap (aluminium).

Solvent for reconstitution

Water for Injections in 1 ml ampoule (Type I glass).

Varilrix must be reconstituted by adding the contents of the supplied container of water for injections diluent to the vial containing the pellet. After the addition of the diluent to the pellet, the mixture should be well shaken until the pellet is completely dissolved in the diluent.

Alcohol and other disinfecting agents must be allowed to evaporate from the skin before injection of the vaccine since they may inactivate the virus.

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