For the use only of Registered Medical Practitioners or a Hospital or a Laboratory
VARILRIX
Varicella Vaccine, Live IP
1. NAME OF THE MEDICINAL PRODUCT
Varicella Vaccine, Live IP.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each dose (0.5 ml) of the reconstituted vaccine contains:
Live attenuated Varicella virus (OKA strain, propagated in MRC5 human diploid cells)….
not less than 103.3 plaque-forming units (PFU)
Water for Injections IP qs 0.5 mL
This vaccine contains a trace amount of neomycin. see section 4.3 Contraindications.
For the full list of excipients, see section 6.1 List of excipients.
VARILRIX meets the World Health Organisation requirements for biological substances
and for varicella vaccines.
3. PHARMACEUTICAL FORM
Powder and solvent for solution for injection.
The powder or pellet of vaccine in the vial is slightly creamy to yellowish or pinkish. The
solvent contained in the syringe or in the ampoule is clear and colorless.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Healthy subjects
VARILRIX is indicated for active immunisation against varicella of healthy subjects and
susceptible healthy close contacts from the age of 12 months onwards.
Susceptible healthy close contacts should be immunised in order to reduce the risk of
transmission of virus to high-risk patients. These include parents and siblings of high-risk
patients, and medical, paramedical personnel and other people who are in close contact
with varicella patients or high-risk patients.
1
4.2 Posology and method of administration
Posology
0.5 ml of reconstituted vaccine contains one immunising dose.
Children from 12 months up to 12 years of age inclusive
It is recommended that 2 doses of VARILRIX be administered to children from 12 months
to 12 years of age in order to ensure optimal protection against varicella. It is preferable
that the second dose be administered at least 6 weeks after the first dose but under no
circumstances less than 4 weeks, after the first dose.
Adolescents 13 years of age or over and adults
Two doses are necessary for subjects from the age of 13. An interval of at least six weeks
should be observed between the two doses, but in no case less than four weeks.
Interchangeability
A single dose of VARILRIX may be administered to subjects 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 intended for subcutaneous injection in the deltoid region of the arm or in the
anterolateral part of the thigh.
For instructions on reconstitution of the medication before administration, see section 6.6
Special precautions for disposal and other handling.
4.3 Contraindications
VARILRIX is contraindicated in subjects with primary or acquired immunodeficiency who
have a total lymphocyte count less than 1200 per mm3 or presenting other evidence of lack
of cellular immune competence, such as subjects with leukemia, lymphomas, blood
dyscrasia, clinically manifest HIV infection, or subjects receiving immunosuppressive
therapy including high dose corticosteroids.
VARILRIX is contraindicated in subjects who have a history of hypersensitivity to any of
the constituents in the vaccine, or to neomycin. However, a history of dermatitis following
contact with neomycin is not a contraindication.
2
VARILRIX is contraindicated in subjects who have shown signs of hypersensitivity after
previous administration of varicella vaccine.
VARILRIX is contraindicated in pregnant women. Pregnancy should be avoided for one
month following vaccination (see section 4.6 Pregnancy and Lactation).
4.4 Special warnings and precautions for use
As for other vaccines, administration of VARILRIX should be postponed in the event of
acute febrile illness. The presence of a minor infection, however, is not a contraindication.
As for any injectable vaccine, it is recommended that an epinephrine solution be available
for injection in the event of a possible anaphylactic reaction (see below, "Treatment in the
event of anaphylactic reaction" under Section 4.8 Undesirable Effects). It is generally
recommended that the vaccinee be kept under medical surveillance for half an hour after
vaccination.
Syncope (fainting) can occur following, or even before any vaccination, with adolescents
in particular, as a psychogenic reaction to injection. This can be accompanied by several
neurological signs such as transient visual disturbances, paraesthesia and tonic-clonic
movements of the limbs during the recovery phase. It is important that measures are in
place to avoid injuries in the event of fainting.
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.
Available data suggest that vaccination within 72 hours of natural exposure to varicella can
alter the clinical course of the disease and even prevent symptoms. The degree of protection
however may be limited (see section 5.1 Pharmacodynamic properties).
As with all vaccines, a protective immune response may not be elicited in all vaccinees. As
with other varicella vaccines, cases of varicella disease have occurred in people who have
previously received VARILRIX. These breakthrough cases are usually mild, with a fewer
number of lesions and less fever as compared to cases occurring in unvaccinated
individuals.
Transmission of the Oka vaccine virus has been shown to occur, but in extremely rare
cases, to seronegative persons in contact with vaccinated persons who have a rash.
However, transmission has not been confirmed in the absence of vaccine-related skin
lesions in the vaccinee.
All contact should be avoided with pregnant women susceptible to contracting varicella
(especially during the first trimester of pregnancy) and with those at high risk for
developing severe varicella (such as leukemia patients or patients receiving
immunosuppressive therapy), especially when the person vaccinated develops a skin
3
eruption within 2 to 3 weeks of immunization. If contact with these persons cannot be
avoided, the potential risk of transmission of the vaccine virus should be weighed against
the risk of acquiring and transmitting the wild varicella virus.
In patients receiving strongly immunosuppressive treatment, clinical varicella has appeared
after vaccination. A virus resembling that of the vaccine has been detected in the vesicles.
In the event of severe clinical signs, antiviral treatment is indicated.
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 intradermally or intravascularly.
Healthy persons living in close contact with patients
To further reduce the risk of infection of high-risk subjects, it is advised that non-immune
persons living in close contact with varicella patients or high-risk patients also be
vaccinated. This category includes parents, brothers and sisters of high-risk subjects,
medical and paramedical personnel and others who live in close contact with these patients.
4.5 Interaction with other medicaments and other forms of interaction
If tuberculin testing has to be performed, 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.
The administration of VARILRIX should be postponed for at least three months after the
administration of immunoglobulins or after a blood transfusion, because the vaccination
may not work properly due to passively acquired varicella antibodies.
Reye's syndrome has been reported after use of salicylates during wild varicella infections.
Consequently, salicylates should not be administered in the 6 weeks following vaccination.
VARILRIX can be administered at the same time as other vaccines. Different injectable
vaccines should always be administered at different injection sites. VARILRIX must never
be mixed with other vaccines in the same syringe. Inactivated vaccines can be administered
at any time relative to the time of administration of VARILRIX.
If VARILRIX is administered after the measles vaccine, an interval at least a month is
recommended, as it is known that vaccination against measles can cause short-term
suppression of the cellular immune response.
4.6 Pregnancy and Lactation
4
Pregnancy
Pregnant women should not be vaccinated with VARILRIX.
However, no harmful effect on the fetus has been documented after administration of
vaccines against varicella to pregnant women.
Pregnancy should be avoided for one month following vaccination. Women intending to
become pregnant should be advised to postpone their plans.
Vaccinated persons who develop a rash within 3 weeks after the vaccination must avoid all
contact with pregnant women (particularly in the first three months of pregnancy).
Lactation
There is insufficient data on the excretion of VARILRIX or on the presence of antibodies
against VARILRIX antigens in breast milk.
A risk for newborns / infants cannot be ruled out.
A decision should be made either to discontinue breastfeeding or to discontinue / abstain
from vaccination with VARILRIX, taking into account the benefit of breastfeeding for the
child with regard to the benefit of prophylaxis against Varicella for the woman.
4.7 Effects on ability to drive and use machines
It is very unlikely that the vaccine has an effect on the capacity to drive a vehicle or to use
machines.
4.8 Undesirable Effects
Clinical trials
Healthy subjects
The safety profile presented below is based on a total of 5369 doses of VARILRIX
administered as monotherapy to children, adolescents and adults.
Undesirable effects with a suspected connection with the vaccine are listed below.
Frequencies are reported as follows:
Very common (≥1/10)
Common (≥1/100, <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
5
Very rare (<1/10,000),
Class of organ systems Frequency Side effects
Upper respiratory infection,
Infections and infestations Uncommon
pharyngitis
Blood and lymphatic
Uncommon Lymphadenopathy
system disorders
Psychiatric disorders Uncommon Irritability
Nervous system disorders Uncommon Headache, somnolence
Eye disorders Rare Conjunctivitis
Respiratory, thoracic and Uncommon
Cough, rhinitis
mediastinal disorders
Uncommon Nausea, vomiting
Gastrointestinal disorders
Rare Abdominal pain, diarrhoea
Common Rash
Skin and subcutaneous
Uncommon Papulo-vesicular eruptions, pruritus
tissue disorders
Rare Urticaria
Musculoskeletal and
Uncommon Arthralgia, myalgia
systemic disorders
Very common Pain, redness at the injection site
Swelling at the injection site *,
fever (oral / axillary temperature≥
General disorders and Common
37.5 °C or rectal temperature≥ 38.0
administration site
ºC) *
conditions
Fever (oral / axillary temperature>
Uncommon 39.0°C or rectal temperature> 39.5°
c), fatigue, malaise
*Swelling at the injection site and fever were reported very commonly in studies conducted
in adolescents and adults. Swelling was also reported very commonly after the second dose
given to children under 13 years of age.
A tendency has been observed toward an increase in reactions of pain, redness and swelling
between the first and the second injection.
No difference was noted in the reactogenicity profile between initially seropositive and
initially seronegative subjects.
Post marketing surveillance
During post-marketing surveillance, the following additional reactions have been reported
after varicella vaccination:
Class of organ systems Frequency Side effects
Herpes zoster *, disseminated
Infections and infestations unknown **
infection by the varicella virus
6
Class of organ systems Frequency Side effects
(vaccine strain) with involvement
of internal organs
Blood and lymphatic
unknown ** Thrombocytopenia
system disorders
Hypersensitivity, anaphylactic
Immune system disorders unknown **
reactions
Encephalitis, cerebrovascular
accident, cerebellitis, cerebellitis
Nervous system disorders unknown ** like symptoms (including transient
gait disturbance and transient
ataxia), convulsions
Vasculitis (including Henoch
Vascular disorders unknown ** Schonlein purpura and Kawasaki
syndrome)
Skin and subcutaneous
unknown ** Erythema multiforme.
tissue disorders
*These reactions reported after vaccinations are also a consequence of infection by the wild
varicella virus. There is no indication of an increased risk of these manifestations after
vaccination compared to the risk incurred with the natural disease.
** Since these events have been notified spontaneously, it is not possible to estimate their
frequency reliably.
Treatment in the event of anaphylactic reaction
Procedure proposed by the “Repertoire Commente des Medicaments (Annotated Repertory
of Medications)” in the event that a severe anaphylactic reaction (associated with
respiratory difficulties, hypotension or shock) occurs.
Treatment is based on epinephrine (adrenalin).
Intramuscular administration is preferable to subcutaneous administration due to better
resorption in the event of hypotension.
The dose of epinephrine is:
− for an adult: 0.2 to 0.5 mL of a 1/ 1000 (= 1 mg/ml) aqueous solution intramuscularly
− for a child: 0.01 mL /kg of a 1/ 1000 (= 1 mg/ml) aqueous solution intramuscularly
(max. 0.3 mL)
If there is no improvement, a second dose can be administered intramuscularly after 5
minutes.
Bronchodilator in the event of bronchospasm; I.V. corticosteroids; plasma substitute in the
event of shock.
7
4.9 Overdose
Cases of accidental administration of doses higher than the recommended dose of
VARILRIX have been reported. Among these cases, the following effects have been
reported: lethargy and convulsions. In the other reported cases of overdose, there were no
related secondary effects.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Viral vaccine, ATC code: J07BK01.
The presence of antibodies after vaccination is recognized as a sign of protection against
the disease.
Efficacy in clinical studies
The efficacy of the GlaxoSmithKline (GSK) vaccines, monovalent Oka (VARILRIX) and
PRIORIX-TETRA [MMRV], in preventing varicella was evaluated in a large, international
randomised study that included the GSK measles-mumps-rubella combined vaccine MMR
(PRIORIX) as the active comparator. The study was conducted in Europe, where
vaccination against varicella is not routine.
Children from 12 to 22 months of age received either two doses of PRIORIX-TETRA at a
6-week interval or one dose of VARILRIX. Vaccine efficacy against confirmed varicella of
any severity and against moderate or severe confirmed varicella was shown after a primary
follow-up period of 2-years (median duration of 3.2 years). In the same study, persistent
efficacy was observed during the long-term follow-up periods of 6-years (median duration
of 6.4 years) and 10 years (median duration of 9.8 years). The data are presented in the
table below:
Group Timing Effectiveness against Efficacy against
confirmed varicella of moderate or severe
any severity confirmed varicella
VARILRIX (1 dose) Year 2 65.4% 90.7%
N =2,487 (97.5% CI: 57. 2, 72.1) (97.5 % CI:85.9,
93.9)
Year 6 (1) 67.0% 90.3%
(95% CI: 61.8, 71.4) (95% CI: 86.9, 92.8)
10 years 67.2% 89.5%
(95% CI: 62.3; 71.5) (95% CI: 86.1; 92.1)
8
Group Timing Effectiveness against Efficacy against
confirmed varicella of moderate or severe
any severity confirmed varicella
Combined vaccine Year 2 94.9% 99.5%
against measles, (97.5% CI: 92.4, 96.6) (97.5% CI: 97.5,
mumps, rubella and 99.9)
chicken pox Year 6 (1) 95.0% 99.0%
(Oka) (2 doses) N = (95% CI: 93.6, 96.2) (95% CI: 97.7, 99.6)
2,489 10 years 95.4% 99.1%
(95% CI: 94.0; 96.4) (95% CI: 97.9; 99.6)
N: number of subjects enrolled and vaccinated
(l)
descriptive analysis
Effectiveness
Data on effectiveness appear to indicate a higher level of protection and a lower incidence
of cases of varicella in those vaccinated after two doses of varicella-containing vaccine
than after a single dose.
The effectiveness of doses of PRIORIX-TETRA in an epidemic situation in day-care centres
in Germany, where routine vaccination against varicella is recommended for children from
the age of 11 months, was 91% (95% CI: 65% -98%) against the disease of any severity
and 94% (95% CI: 54%-99%) against the moderate disease.
The effectiveness of a dose of VARILRIX was assessed in different contexts (epidemic,
case analysis and database studies) and varied from 20% to 92% against any type of
varicella and from 86% to 100% against the moderate or severe disease.
Immune response
In children 11 months to 21 months of age, the seroconversion rate measured with ELISA,
Enzygnost, Dade Behring (50 mIU/ml) six weeks reached 89.6% after administration of
one dose of vaccine, and 100% after administration of a second dose of vaccine.
In children from 9 months to 12 years of age inclusive, the seroconversion rate measured
by immunofluorescence six weeks after administration of a dose of vaccine exceeded 98%.
In children from 9 months to 6 years of age, the seroconversion rate measured by
immunofluorescence six weeks after administration of a second dose of vaccine was 100%.
A marked increase in antibody titers was observed following administration of a second
dose (5 to 26-fold GMT increase).
In subjects 13 years of age and over, the seroconversion rate measured by
immunofluorescence six weeks after administration of a second dose of vaccine was 100%.
One year after vaccination, all subjects tested were still seropositive.
9
In clinical studies, efficacy data show a higher level of protection and a reduction in the
number of varicella cases appearing after administration of two doses of vaccine instead of
a single dose.
Published data on the prevention of varicella within 3 days after exposure to the varicella
virus are limited. In a randomized, double-blind, placebo-controlled study involving 42
children aged 12 months to 13 years, 22 children received the dose of VARILRIX and 20
children received placebo. Similar percentages (respectively 41% and 45%) of children
contracted varicella, but the risk of developing a moderate to severe form of the disease
was eight times higher in the placebo group compared to the vaccinated group (relative
risk. = 8.0, 95% CI 1.2-51.5, P: 0.003) (see section 4.4 Special warnings and precautions
for use).
5.2 Pharmacokinetic Properties
Evaluation of the pharmacokinetic properties is not required for vaccines.
5.3 Preclinical Safety Data
Not relevant.
6. PHARMACEUTICAL PARTICULARS
6.1 List of Excipients
Powder: Anhydrous Lactose, Sorbitol, Mannitol, Amino acids
Solvent: Water for injectable preparations.
Neomycin sulphate is present as a residual from the manufacturing process.
6.2 Incompatibilities
VARILRIX should not be mixed with other vaccines in the same syringe.
6.3 Shelf-life
24 months.
The reconstituted vaccine can be kept for 90 minutes maximum at room
temperature (25° C) or kept in a refrigerator (+2° to +8°C) for 8 hours maximum.
If the reconstituted vaccine is not used within these periods of time, it should be
discarded.
The expiry date is indicated on the label and packaging.
10
6.4 Special precautions for storage
VARILRIX should be kept in a refrigerator (between 2° C and 8° C).
For storage conditions after reconstitution of the medicinal product, see section 6.3 Shelf
life.
Keep out of reach of children.
6.5 Nature and contents of container
Box containing a single-dose vial of vaccine accompanied by a pre-filled syringe or an
ampoule of solvent. The containers are of Type I neutral glass (European Pharmacopeia).
All presentations may not be marketed in India.
6.6 Special precautions for disposal and other handling
Small pH variations can cause the color of the reconstituted vaccine to vary from pale
peach to pink without changing the quality of the vaccine.
Before administration, inspect the solvent and the reconstituted vaccine visually to detect
any foreign particles and/or any change in the physical appearance prior to reconstitution
or administration. In the event of either being observed, do not use the solvent or the
reconstituted vaccine.
Instructions for reconstitution of the vaccine with the solvent presented in ampoules
VARILRIX should be reconstituted by adding the entire contents of the ampoule of solvent
supplied to the vial of powder. The mixture should be well shaken until the powder is
completely dissolved.
The vaccine should be used rapidly after reconstitution.
Withdraw the entire contents of the vial.
A new needle must be used to administer the vaccine.
Instructions for reconstitution of the vaccine with the solvent presented in a pre-filled
syringe.
VARILRIX is reconstituted by adding the entire contents of the pre-filled syringe of solvent
to the vial containing the powder.
11
To attach the needle to the syringe, please read the instructions in Figure 1 and 2 carefully.
Note however that the syringe supplied with VARILRIX may differ slightly (without
threading) from the syringe described in the drawing
In this case, the needle should not be screwed in for attachment to the syringe.
Base
Needle Needle protector
Syringe Luer Lock Adaptor
Plunger
Barrel
Cap
Figure 1 Figure 2
Always hold the syringe by the barrel, not the plunger or the Luer Lock Adaptor (LLA),
and keep the needle in line with the syringe (see Figure 2). Failure to comply with this
instruction could cause deformation of or leakage from the LLA.
During assembly of the syringe, if the LLA becomes detached, a new dose of vaccine must
be used (new syringe and new vial).
1. Unscrew the syringe cap by turning it anticlockwise (see Figure 1).
Whether the LLA turns or not, please follow the steps below:
2. Attach the needle to the syringe by carefully placing the needle base in the LLA and
rotating it one quarter turn clockwise until you feel it is locked (see Figure 2).
3. Remove the needle protector, can be a little difficult.
4. Add the solvent to the powder. The mixture should be well shaken until the powder is
completely dissolved in the solvent.
The vaccine should be used promptly after the reconstitution.
5. Withdraw the entire contents of the vial.
12
6. A new needle should be used to administer the vaccine. Unscrew the needle from the
syringe and attach the needle for injection by repeating step 2 above.
Any unused medicinal product or waste material should be disposed of in accordance with
local regulations.
7. MARKETING AUTHORISATION HOLDER
GlaxoSmithKline Pharmaceuticals Limited,
Registered office
Dr. Annie Besant Road, Worli
Mumbai 400 030, India.
8. MARKETING AUTHORISATION NUMBER(S)
File no. :12-70/96-DC
9. DATE OF FIRST AUTHORISATION/ RENEWAL OF THE
AUTHORISATION
Date of first authorization: 19th June 1998.
For further information please contact:
GlaxoSmithKline Pharmaceuticals Limited.
Registered office
Dr. Annie Besant Road, Worli
Mumbai 400 030, India.
Trademarks are owned by or licensed to the GSK group of companies.
Version: VRX/PI/IN/2022/02 dated 04-Aug-2022.
Adapted from Belgian SPC approved on 19-Mar-2020 [GDS 13/ IPI 15 dated 08-May-
2018 and GDS 14/IPI 16 dated 11-Dec-2018].
13
