Varilrix

Varilrix

vaccine, varicella-zoster

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig
/
Agencia Lei Va Hong
Full Prescribing Info
Contents
Live attenuated Oka strain varicella-zoster virus.
Description
A 0.5ml dose of the reconstituted vaccine contains not less than 103.3 plaque-forming units (PFU) of the varicella-zoster virus.
VARILRIX is a lyophilised preparation of the live attenuated Oka strain of varicella-zoster virus, obtained by propagation of the virus in MRC5 human diploid cell culture.
VARILRIX meets the World Health Organisation requirements for biological substances and for varicella vaccines.
The powder is slightly cream to yellowish or pinkish.
The solvent is clear and colourless.
Excipients/Inactive Ingredients: Powder: amino acids, human albumin, lactose, mannitol, sorbitol.
Solvent: water for injections.
Residues: neomycin sulphate.
Action
Pharmaco-therapeutic group: Viral vaccines. ATC code: J07BK01.
Pharmacology: Pharmacodynamics: Mechanism of action: VARILRIX produces an attenuated clinically inapparent varicella infection in susceptible subjects.
The presence of antibodies is accepted to be an indication of protection.
Pharmacodynamic effects: Efficacy and effectiveness: The efficacy of GlaxoSmithKline (GSK)'s Oka/RIT varicella vaccines in preventing confirmed varicella disease (by polymerase chain reaction {PCR} or exposure to a varicella case) has been evaluated in a large active controlled clinical trial in which children aged 12-22 months received one dose of VARILRIX or two doses of combined measles, mumps, rubella and varicella (Oka/RIT) vaccine. Vaccine efficacy against confirmed varicella of any severity and against moderate or severe confirmed varicella observed after a primary follow-up period of 2 years (median duration 3.2 years) and after an extended follow-up period of 6 years (median duration 6.4 years) are presented in the Table as follows. (See Table 1.)

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In another randomised placeo-controlled trial conducted in children (n=327) 12 - 30 months of age one dose of VARILRIX vaccine was administered and followed up for an average of 29.3 months. The protective efficacy against common clinical cases of varicella was 100% and against clinical varicella of any severity was calculated as 88% (95% CI 72-96). The median number of vesicles in breakthrough cases in children was 2 (placebo group median = 30).
In a randomised placeo-controlled trial conducted in adults (n=233) two doses of VARILRIX vaccine were administered at an interval of 2 months and then followed up for an average of 18 months. Efficacy against clinical varicella of any severity was conservatively estimated at 75.9% (95% CI 43.8-89.7); errors in the methodology used in this trial imply that efficacy cannot be accurately determined. Of the 11 vaccinees with breakthrough disease, only 2 had >200 vesicles, compared with 57% of the unvaccinated subjects.
In both trials, subjects who responded to vaccination and who later developed breakthrough varicella had fewer lesions than unvaccinated individuals, demonstrating attenuation of varicella infection for those subjects who were not protected completely.
In a 3 year follow-up study, lower incidences of varicella breakthrough cases were reported in the group receiving two-doses of PRIORIX-TETRA (1 case, 0.44%) than in the group receiving only one dose of VARILRIX (4 cases, 5.06%), however the number of breakthrough cases were too small to make any conclusion about comparative vaccine efficacy. No cases of measles, mumps or rubella breakthrough disease were reported in any group during this 3 years follow-up.
Effectiveness studies: Effectiveness data suggest a higher level of protection and a decrease in breakthrough varicella following two doses of vaccine than following one dose.
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 in a study performed in Uruguay were respectively 81% and 87% overall.
Immune response: Healthy subjects: In children aged 9 months to 12 years, the overall seroconversion rate was >98% when measured at 6 weeks after vaccination with one dose. In children 12-15 months of age, antibodies persisted for at least 7 years after vaccination with one dose.
In children aged 9 months to 6 years, the seroconversion rate was 100% when measured 6 weeks after vaccination with a second dose. A marked increase of antibody titres was observed following the administration of a second dose (5 to 26-fold GMT increase).
In subjects aged 13 years and above the seroconversion rate was 100% when measured 6 weeks after the second dose. One year after vaccination, all subjects tested were still seropositive.
In clinical trials, the majority of vaccinated subjects who were subsequently exposed to wild-type virus were either completely protected from clinical chickenpox or developed a milder form of the disease (i.e. low number of vesicles, absence of fever).
There are insufficient data to assess the rate of protection against complications of chickenpox such as encephalitis, hepatitis or pneumonia.
High-risk patients: There are only very limited data from clinical trials available in patients at high risk of varicella. The overall seroconversion rate in these patients was found to be ≥ 80%.
In high-risk patients, periodic measurement of varicella antibodies after immunisation may be indicated in order to identify those who may benefit from re-immunisation.
Clinical studies: See "Pharmacodynamic effects".
Pharmacokinetics: Evaluation of pharmacokinetic properties is not required for vaccines.
Indications/Uses
Healthy subjects: VARILRIX is indicated for active immunisation against varicella of healthy subjects from 9 months of age.
Groups who would particularly benefit from vaccination include: Non-immune adults, especially those in at-risk occupations such as health care workers, teachers and workers in children's day-care centres; Non-immune parents of young children; Non-immune household contacts, both adults and children, of immunocompromised patients with no history of the disease.
Dosage/Direction for Use
0.5ml of reconstituted vaccine contains one immunizing dose.
Posology: Healthy subjects: Children 9 months up to and including 12 years of age: Children from the age 9 months up to and including 12 years of age should receive 2 doses of VARILRIX to ensure optimal protection against varicella (see Pharmacology: Pharmacodynamics: Pharmacodynamic Effects under Actions).
It is preferable to administer the second dose at least 6 weeks after the first dose.
Adolescents and adults from 13 years of age and above: From 13 years of age and above: 2 doses. It is preferable to administer the second dose at least 6 weeks after the first dose.
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 for subcutaneous administration in the deltoid region or in the anterolateral area of the thigh.
For instructions on reconstitution of the medicinal product before administration see Cautions for Usage.
Overdosage
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.
Contraindications
VARILRIX is contraindicated in subjects with severe humoral or cellular immunodeficiency such as: Subjects with primary or acquired 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. subjects with leukaemias, lymphomas, blood dyscrasias, clinically manifest HIV infection); Subjects receiving immunosuppressive therapy including high dose of corticosteroids.
See also Precautions.
VARILRIX is contraindicated in subjects with known hypersensitivity to neomycin or to any other component of the vaccine. 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.
VARILRIX is contraindicated in pregnant women. Pregnancy should be avoided for one month after vaccination (see Use in Pregnancy & Lactation).
Special Precautions
As with other vaccines, the administration of VARILRIX should be postponed in subjects suffering from acute severe febrile illness. In healthy subjects the presence of a minor infection, however, is not a contra-indication for 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.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of 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.
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 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.
The mild nature of the rash in the healthy contacts indicates that the virus remains attenuated after passage through human hosts.
There is limited data on the use of VARILRIX 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 varicella despite appropriate vaccine administration. Immunocompromised subjects should be monitored carefully for signs of varicella.
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.
Use In Pregnancy & Lactation
Fertility: No data available.
Pregnancy: Pregnant women must not be vaccinated with VARILRIX. 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 VARILRIX during pregnancy are not available and animal studies on reproductive toxicity have not been conducted.
Lactation: There are no data regarding use in breastfeeding women.
Adverse Reactions
Clinical trial data: Healthy subjects: More 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 5,369 doses of VARILRIX administered in monotherapy to children, adolescents and adults.
Adverse reactions reported are listed according to the following frequency: Very common: ≥1/10; Common: ≥1/100 to < 1/10; Uncommon: ≥1/1000 to <1/100; Rare: ≥1/10000 to <1/1000; Very rare: < 1/10000. (See Table 2.)

Click on icon to see table/diagram/image

A trend for higher incidence of pain, redness and 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.
High-risk patients: There are only very limited data from clinical trials available in patients at high risk of severe varicella. However, vaccine-associated reactions (principally papulo-vesicular eruptions and fever) are usually mild. As in healthy subjects, redness, swelling and pain at the site of injection are mild and transient.
Post-marketing data: During post-marketing surveillance, the following additional reactions have been reported after varicella vaccination: (See Table 3.)

Click on icon to see table/diagram/image
Drug Interactions
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 subjects who have received immune globulins 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.
Healthy subjects: VARILRIX can be administered at the same time as any other vaccines. Different injectable vaccines should always be administered at different injection sites.
Should a measles containing vaccine not be given at the same time as VARILRIX, it is recommended that an interval of at least one month should be respected since it is recognised that measles vaccination may lead to short lived suppression of the cell mediated immune response.
High-risk patients: 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 contra-indication has been established. However, different injectable vaccines should always be administered at different injection sites.
Caution For Usage
Use and Handling: Due to minor variations of its pH, the colour of the reconstituted vaccine may vary from peach to pink coloured solution.
The solvent and the reconstituted vaccine should be inspected visually for any foreign particulate matter and/or variation of physical aspect prior to administration. In the event of either being observed, discard the solvent or the reconstituted vaccine.
Instructions for reconstitution of the vaccine with solvent presented in ampoules: VARILRIX must be reconstituted by adding the contents of the supplied container 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: VARILRIX must be reconstituted by adding the entire content of the pre-filled syringe of solvent to the vial containing the powder.
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 it lock.
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.
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.
Incompatibilities: VARILRIX should not be mixed with other vaccines in the same syringe.
Storage
The lyophilised vaccine should be stored in a refrigerator between +2°C and +8°C. The solvent can be stored in the refrigerator or at ambient temperatures (maximum 25°C). The lyophilised vaccine is not affected by freezing.
When supplies of VARILRIX are distributed from a central cold store, transport must be done under refrigerator conditions especially in hot climates.
After reconstitution, it is recommended that the vaccine be injected as soon as possible. (See "Shelf-Life").
Shelf-life: It has been demonstrated that the reconstituted vaccine may be kept for up to 90 minutes at room temperature (25°C) and up to 8 hours in the refrigerator (2°C-8°C).
ATC Classification
J07BK01 - varicella, live attenuated ; Belongs to the class of varicella viral vaccines.
Presentation/Packing
Vial (lyophilised, slightly cream to yellowish or pinkish coloured powd) 0.5 mL x 1's.
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