- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Children 1-12 years, adolescents (≥ 13 years) and adultsTwo doses (each of 0.5 ml of reconstituted vaccine) should be given, with an interval between doses of at least 6 weeks but in no circumstances less than 4 weeks.One dose of Varilrix may be administered after a first dose of another varicella containing vaccine (see section 5.1).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).Varilrix should not be administered to children aged less than one year.
ElderlyThere are no data on immune responses to Varilrix in the elderly.
Method of administrationVarilrix 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.Varilrix must not be mixed with any other medicinal product in the same syringe (see also sections 4.5 and 6.2).
Transmission of the vaccine viral strainTransmission 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.The Oka vaccine viral strain has recently been shown to be sensitive to acyclovir.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.
PregnancyPregnant women should not be vaccinated with Varilrix..However, fetal damage has not been documented when varicella vaccines have been given to pregnant women.Pregnancy should be avoided for 1 month following vaccination. Women who intend to become pregnant should be advised to delay.
LactationThe infants of seronegative women would not have acquired transplacental antibody to varicella-zoster virus. Therefore, due to the theoretical risk of transmission of the vaccine viral strain from mother to infant, women should not be vaccinated while breastfeeding.
FertilityNo fertility data are available
Clinical trials in healthy subjectsMore than 7,900 individuals have participated in clinical trials evaluating the reactogenicity profile of the vaccine administered alone or concomitantly with other vaccines.The safety profile presented below is based on a total of 5369 doses of Varilrix administered alone to children, adolescents and adults.The most common adverse reactions observed after vaccine administration were injection site pain (23.8%), redness (19.9%) and swelling (12.1%).Frequencies are reported as:
|Common:||≥1% and <10%|
|Uncommon:||≥0.1% and <1%|
|Rare:||≥0.01% and <0.1%|
Blood and lymphatic system disordersUncommon: lymphadenopathy
Nervous system disordersUncommon: headache, somnolenceVery rare: dizziness
Eye disordersRare: conjunctivitis
Respiratory, thoracic and mediastinal disordersUncommon: cough, rhinitis
Gastrointestinal disordersUncommon: nausea, vomitingRare: abdominal pain, diarrhoea
Skin and subcutaneous tissue disordersCommon: rashUncommon: varicella-like rash, pruritus Rare: urticaria
Musculoskeletal and connective tissue disordersUncommon: arthralgia, myalgia
Infections and infestationsUncommon: upper respiratory tract infection, pharyngitis
General disorders and administration site conditionsVery common: pain, redness and swelling at the injection site*, fever (oral/axillary temperature ≥ 37.5°C or rectal temperature ≥ 38.0°C)*Uncommon: fever (oral/axillary temperature > 39.0°C or rectal temperature > 39.5°C), fatigue, malaiseVery rare: face oedema
Psychiatric disordersUncommon: irritability* Swelling at the injection site and fever were commonly reported in studies conducted in children ≤ 12 years.In general, the reactogenicity profile after the second dose was comparable to that after the first dose. However, the rates of injection site reactions (primarily redness and swelling) were higher after the second dose in children aged ≤12 years.No differences were seen in the reactogenicity profile between initially seropositive and initially seronegative subjects.
Nervous system disordersFebrile and non-febrile convulsions cerebellar ataxia**
Infections and infestationsHerpes zoster**
Immune system disordersHypersensitivity, anaphylactic reactions** This reaction reported after vaccination is also a consequence of wild-type varicella infection. There is no indication of an increased risk of its occurrence following vaccination compared with wild-type disease.Transmission of the vaccine virus from healthy vaccinees to healthy contacts has been shown to occur very rarely.
Reporting of suspected adverse reactionsReporting 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.
Efficacy and effectivenessThe efficacy of GlaxoSmithKline (GSK)'s monovalent Oka/RIT (Varilrix) and Priorix-Tetra vaccines in preventing varicella disease has been evaluated in a large randomised clinical trial, which included GSK combined measles-mumps-rubella vaccine, Priorix as control. The trial has been conducted in European countries where no routine varicella vaccination is implemented. Children aged 12-22 months received two doses of Priorix-Tetra six weeks apart (N = 2279) or one dose of Varilrix (N = 2263) and were followed up for a period of approximately 35 months post vaccination (long term 10-year follow-up ongoing). The observed vaccine efficacy against epidemiologically confirmed or PCR (Polymerase Chain Reaction) confirmed Varicella of any severity (defined using a prespecified scale) was 94.9% (97.5% CI: 92.4; 96.6%) after two doses of Priorix-Tetra and 65.4 % (97.5% CI: 57.2;72.1%) after one dose of Varilrix. Vaccine efficacy against moderate or severe confirmed varicella was 99.5% (97.5% CI: 97.5;99.9%) after two doses of Priorix-Tetra and 90.7% (97.5% CI: 85.9; 93.9%) after one dose of Varilrix .In a study in Finland specifically designed to evaluate vaccine efficacy of Varilrix, 493 children 10 to 30-month-old were followed up for a period of approximately 2.5 years after vaccination with one dose. The protective efficacy was 100% (95% CI: 80;100%) against common or severe clinical cases of varicella ( ≥ 30 vesicles) and 88% (95% CI: 72;96) against any serological confirmed case of varicella (at least 1 vesicle or papule).The effectiveness of one dose of Varilrix was estimated in different settings (outbreaks, case-control and database studies) and ranged from 20%-92% against any varicella disease and from 86%-100% against moderate or severe disease. The impact of one dose of Varilrix in reducing varicella hospitalizations and ambulatory visits among children were respectively 81% and 87% overall.Effectiveness data suggest a higher level of protection and a decrease in breakthrough varicella following two doses of vaccine than following one dose.In clinical trials that enrolled 211 adolescents and 213 adults, 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.Virtually all (≥98.7%) children aged 9 months to 12 years tested had antibody levels ≥ 4 (dil-1) six weeks after immunisation with one dose of Varilrix.All of 659 children aged 9 months to 6 years, who received a second dose of Varilrix or received Varilrix after a first dose of another varicella vaccine, had antibody levels ≥ 4 (dil-1) at 6-18 weeks following vaccination. There was a large increase in GMT (up to 13-fold) between post-dose 1 and post-dose 2.However, the safety and immunogenicity of a second dose of Varilrix in adolescents (≥13 years) and adults primed with another varicella-containing vaccine has not been specifically studied in clinical trials.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.The percentage of vaccinees who will later experience herpes-zoster due to reactivation of the Oka strain virus is currently unknown. However, the risk of zoster after vaccination is currently thought to be much lower than would be expected after wild-type virus infection, due to attenuation of the vaccine strain.
Instructions for reconstitution of the vaccine with diluent presented in ampoulesVarilrix must be reconstituted by adding the entire contents of the supplied ampoule of water for injections diluent to the vial containing the powder. After the addition of the diluent to the powder, the mixture should be well shaken until the pellet is completely dissolved in the diluent.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.Alcohol and other disinfecting agents must be allowed to evaporate from the skin before injection of the vaccine since they may inactivate the virus.
Instructions for reconstitution of the vaccine with diluent presented in pre-filled syringeVarilrix must be reconstituted by adding the entire content of the pre-filled syringe of diluent to the vial containing the powder.To attach the needle to the syringe, refer to the below drawing. However, the syringe provided with Varilrix might be slightly different (without screw head) than the syringe described in the drawing. In that case, the needle should be attached without screwing. 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 diluent to the powder. After the addition of 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.A new needle should be used to administer the vaccine.Withdraw the entire contents of the vial.Alcohol and other disinfecting agents must be allowed to evaporate from the skin before injection of the vaccine since they may inactivate the virus.Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Trading as :GlaxoSmithKline UKStockley Park WestUxbridge Middlesex UB11 1BTUnited Kingdom
|Vaccine :||PL 10592/0121|
|Diluent :||PL 10592/0021|
Stockley Park West, Uxbridge, Middlesex, UB11 1BT
+44 (0)208 990 4328
+44 (0)800 221 441