4.1. Therapeutic indications

Varilrix is indicated for active immunisation against varicella:

- In healthy individuals from 9 to 11 months of age (see section 5.1), under special circumstances;

- In healthy individuals from the age of 12 months (see section 5.1);

- For post-exposure prophylaxis if administered to healthy, susceptible individuals exposed to varicella within 72 hours of contact (see sections 4.4 and 5.1);

- In individuals at high risk of severe varicella (see sections 4.3, 4.4 and 5.1).

The use of Varilrix should be based on official recommendations.

4.2. Posology and method of administration

Posology

The immunisation schedules for Varilrix should be based on official recommendations.

Healthy individuals

Infants from 9 months to 11 months of age (inclusive)

Infants from 9 to 11 months of age (inclusive) receive two doses of Varilrix to ensure optimal protection against varicella (see section 5.1). The second dose should be given after a minimum interval of 3 months.

Children from 12 months of age, adolescents and adults

Children from the age of 12 months as well as adolescents and adults receive two doses of Varilrix to ensure optimal protection against varicella (see section 5.1). The second dose should generally be given at least 6 weeks after the first dose. Under no circumstances should the interval between the doses be less than 4 weeks.

Individuals at high risk of severe varicella

Individuals at high risk of severe varicella may benefit from re-vaccination following the 2-dose schedule (see section 5.1). Periodic measurement of varicella antibodies after immunisation may be indicated in order to identify those who may benefit from re-immunisation. Under no circumstances should the interval between the doses be less than 4 weeks.

Other paediatric population

The safety and efficacy of Varilrix in infants less than 9 months of age have not yet been established. No data are available.

Interchangeability

- A single dose of Varilrix may be administered to those who have already received a single dose of another varicella-containing vaccine.

- A single dose of Varilrix may be administered followed by a single dose of another varicella-containing vaccine.

Method of administration

Varilrix is to be injected subcutaneously (SC) or intramuscularly (IM) in the deltoid region or in the anterolateral area of the thigh.

Varilrix should be administered subcutaneously in individuals with bleeding disorders (e.g. thrombocytopenia or any coagulation disorder).

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

4.3. Contraindications

Varilrix is contraindicated in individuals with severe humoral or cellular (primary or acquired) immunodeficiency such as (see also section 4.4.):

- subjects with immunodeficiency states with a total lymphocyte count less than 1,200 per mm3;

- subjects presenting other evidence of lack of cellular immune competence (e.g. patients with leukaemias, lymphomas, blood dyscrasias, clinically manifest HIV infection);

- subjects on current immunosuppressive therapy (including high doses of corticosteroids). Varilrix is not contraindicated in individuals who are receiving topical or low-dose parenteral corticosteroids (e.g. for asthma prophylaxis or replacement therapy);

- severe combined immunodeficiency;

- agammaglobulinemia;

- AIDS or symptomatic HIV infection or an age-specific CD4+ T-lymphocyte percentage in children below 12 months: CD4+ <25%; children between 12-35 months: CD4+ < 20%; children between 36-59 months: CD4+ < 15%.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to neomycin. However, a history of contact dermatitis to neomycin is not a contraindication.

Varilrix is contraindicated in subjects having shown signs of hypersensitivity after previous administration of varicella vaccine.

Pregnancy. Furthermore, pregnancy should be avoided for 1 month following vaccination (see section 4.6).

4.4. Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

As with other vaccines, the administration of Varilrix 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 especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic reaction 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.

Limited protection against varicella may be obtained by vaccination up to 72 hours after exposure to natural disease (see section 5.1).

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 Varilrix. These breakthrough cases are usually mild, with a fewer number of lesions and less fever as compared to cases in unvaccinated individuals.

Transmission

Transmission of the Oka varicella vaccine virus has been shown to occur at a very low rate in seronegative contacts of vaccinees with rash. Transmission of the Oka varicella vaccine virus from a vaccinee who does not develop a rash to seronegative contacts cannot be excluded.

Compared to healthy vaccinees, leukaemia patients are more likely to develop a papulovesicular rash (see also section 4.8). In these cases too, the course of the disease in the contacts was mild.

Vaccine recipients, even those who do not develop a varicella-like rash, should attempt to avoid contact, whenever possible, with high-risk individuals susceptible to varicella for up to 6 weeks following vaccination. In circumstances where contact with high-risk individuals susceptible to varicella is unavoidable, the potential risk of transmission of the varicella vaccine virus should be weighed against the risk of acquiring and transmitting wild-type varicella virus.

High-risk individuals susceptible to varicella include:

- Immunocompromised individuals (see sections 4.3 and 4.4);

- Pregnant women without documented positive history of varicella (chickenpox) or laboratory evidence of prior infection;

- Newborns of mothers without documented positive history of chickenpox or laboratory evidence of prior infection.

The mild nature of the rash in the healthy contacts indicates that the virus remains attenuated after passage through human hosts.

Individuals at high risk of severe varicella

There is only limited data from clinical trials available for Varilrix (+4°C formulation) in individuals at high risk of severe varicella.

Vaccination may be considered in patients with selected immune deficiencies where the benefits outweigh the risks (e.g. asymptomatic HIV subjects, IgG subclass deficiencies, congenital neutropenia, chronic granulomatous disease, and complement deficiency diseases).

Immunocompromised patients who have no contraindication for this vaccination (see section 4.3) may not respond as well as immunocompetent subjects, therefore some of these patients may acquire varicella in case of contact, despite appropriate vaccine administration. These patients should be monitored carefully for signs of varicella.

Should vaccination be considered in individuals at high risk of severe varicella, it is advised that:

- maintenance chemotherapy should be withheld one week before and one week after immunisation of patients in the acute phase of leukaemia. Patients under radiotherapy should normally not be vaccinated during the treatment phase. Generally, patients are immunised when they are in complete haematological remission from their disease.

- the total lymphocyte count should be at least 1,200 per mm3 or no other evidence of lack of cellular immune competence exists.

- vaccination should be carried out a few weeks before the administration of the immunosuppressive treatment for patients undergoing organ transplantation (e.g. kidney transplant).

Very few reports exist on disseminated varicella with internal organ involvement following vaccination with Oka varicella vaccine strain mainly in immunocompromised subjects.

Varilrix must not be administered intravascularly or intradermally.

Encephalitis

Encephalitis has been reported during post-marketing use of live attenuated varicella vaccines. In a few cases fatal outcomes have been observed, especially in patients who were immunocompromised (see section 4.3). Vaccinees/parents should be instructed to seek prompt medical attention if they/their child experience, after vaccination, symptoms suggestive of encephalitis such as loss or reduced levels of consciousness, convulsions or ataxia accompanied by fever and headache.

Phenylalanine content

The vaccine contains 331 micrograms of phenylalanine per dose. Phenylalanine may be harmful for individuals with phenylketonuria (PKU).

4.5. Interaction with other medicinal products and other forms of interaction

If tuberculin testing has to be done it should be carried out before or simultaneously with vaccination since it has been reported that live viral 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 individuals who have received immunoglobulins or a blood transfusion, vaccination should be delayed for at least three months because of the likelihood of vaccine failure due to passively acquired varicella antibodies.

Salicylates should be avoided for 6 weeks after varicella vaccination as Reye's Syndrome has been reported following the use of salicylates during natural varicella infection.

Use with other vaccines

Healthy individuals

Clinical studies with varicella-containing vaccines support concomitant administration of Varilrix with any of the following monovalent or combination vaccines: measles-mumps-rubella vaccine (MMR), diphtheria-tetanus-acellular pertussis vaccine (DTPa), reduced antigen diphtheria-tetanus-acellular pertussis vaccine (dTpa), Haemophilus influenzae type b vaccine (Hib), inactivated polio vaccine (IPV), hepatitis B vaccine (HBV), hexavalent vaccine (DTPa-HBV-IPV/Hib), hepatitis A vaccine (HAV), meningococcal serogroup B vaccine (Bexsero), meningococcal serogroup C conjugate vaccine (MenC), meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY) and pneumococcal conjugate vaccine (PCV).

Different injectable vaccines should always be administered at different injection sites.

If a measles vaccine is not given at the same time as Varilrix, there should be an interval of at least one month between the administration of these vaccines as the measles vaccine may lead to short-term suppression of the cellular immune response.

Individuals at high risk of severe varicella

Varilrix should not be administered at the same time as other live attenuated vaccines. Inactivated vaccines may be administered in any temporal relationship to Varilrix, given that no specific contraindication has been established. However, different injectable vaccines should always be administered at different injection sites.

4.6. Fertility, pregnancy and lactation

Pregnancy

Pregnant women should not be vaccinated with Varilrix.

However, foetal damage has not been documented when varicella vaccines have been given to pregnant women.

Women of child-bearing potential

Pregnancy should be avoided for 1 month following vaccination. Women who intend to become pregnant should be advised to delay.

Breast-feeding

There are no data regarding use in breast-feeding women.

Due to the theoretical risk of transmission of the vaccine viral strain from mother to infant, Varilrix is generally not recommended for breast-feeding mothers (see also section 4.4). Vaccination of exposed women with negative history of varicella or known to be seronegative to varicella should be assessed on an individual basis.

Fertility

No data available.

4.7. Effects on ability to drive and use machines

No studies on the effects of Varilrix on the ability to drive and use machines have been performed. Varilrix has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 “Undesirable effects” may temporarily affect the ability to drive or use machines.

4.8. Undesirable effects

Clinical trial data

Healthy individuals

More than 7,900 individuals have participated in clinical trials evaluating the reactogenicity profile of the vaccine administered subcutaneously either alone or concomitantly with other vaccines.

The safety profile presented below is based on a total of 5,369 doses of Varilrix administered alone to infants, children, adolescents and adults.

Adverse reactions reported are listed according to the following frequency:

Very common:

Common:

Uncommon:

Rare:

Very rare:

(≥ 1/10)

(≥ 1/100 to < 1/10)

(≥ 1/1 000 to < 1/100)

(≥ 1/10 000 to < 1/1 000)

(< 1/10 000)

Within each frequency grouping the adverse reactions are presented in the order of decreasing seriousness.

System organ class∗

Frequency

Adverse reactions

Infections and infestations

Uncommon

upper respiratory tract infection, pharyngitis

Blood and lymphatic system disorders

Uncommon

lymphadenopathy

Psychiatric disorders

Uncommon

irritability

Nervous system disorders

Uncommon

headache, somnolence

Eye disorders

Rare

conjunctivitis

Respiratory, thoracic and mediastinal disorders

Uncommon

cough, rhinitis

Gastrointestinal disorders

Uncommon

vomiting, nausea

Rare

diarrhoea, abdominal pain

Skin and subcutaneous tissue disorders

Common

rash

Uncommon

viral rash, pruritus

Rare

urticaria

Musculoskeletal and connective tissue disorders

Uncommon

arthralgia, myalgia

General disorders and administration site conditions

Very common

pain, erythema

Common

pyrexia (oral/axillary temperature ≥ 37.5°C or

rectal temperature ≥ 38.0°C) †, injection site swelling†

Uncommon

pyrexia (oral/axillary temperature > 39.0°C or rectal temperature > 39.5°C),

fatigue, malaise

∗ According to MedDRA (Medical Dictionary for Regulatory Activities) terminology

† Injection site swelling and pyrexia were reported very commonly in studies conducted in adolescents and adults. Injection site swelling was also reported very commonly after the second dose in children under 13 years of age.

A trend for higher incidence of pain, erythema and injection site swelling after the second dose was observed as compared to the first dose.

No differences were seen in the reactogenicity profile between initially seropositive and initially seronegative subjects.

In a clinical trial, 328 children aged 11 to 21 months received GlaxoSmithKline (GSK)'s combined measles, mumps, rubella and varicella vaccine (containing the same varicella strain as Varilrix) either by subcutaneous or intramuscular route. A comparable safety profile was observed for both administration routes.

Individuals at high risk of severe varicella

There are limited data from clinical trials available in subjects at high risk of severe varicella. However, vaccine-associated reactions (mainly papulo-vesicular eruptions and pyrexia) are usually mild. As in healthy subjects, erythema, swelling and pain at the site of injection are mild and transient.

Post-marketing data

The following additional adverse reactions have been identified in rare occasions during post-marketing surveillance. Because they are reported voluntarily from a population of unknown size, a true estimate of frequency cannot be provided.

System organ class∗

Adverse reactions

Infections and infestations

herpes zoster

Blood and lymphatic system disorders

thrombocytopenia

Immune system disorders

anaphylactic reaction, hypersensitivity

Nervous system disorders

encephalitis†, cerebrovascular accident, seizure, cerebellitis, cerebellitis like symptoms (including transient gait disturbance and transient ataxia)

Vascular disorders

vasculitis (including Henoch Schonlein purpura and Kawasaki syndrome)

Skin and subcutaneous tissue disorders

erythema multiforme

∗ According to MedDRA (Medical Dictionary for Regulatory Activities) terminology

† See description of selected adverse reactions

Description of selected adverse reactions

Encephalitis has been observed following vaccination with live attenuated varicella vaccines. Fatal outcome was reported in a few cases, especially in immunocompromised people (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Cases of accidental administration of more than the recommended dose of Varilrix have been reported. Amongst these cases, the following adverse events were reported: lethargy and convulsions. In the other cases reported as overdose there were no associated adverse events.