For the use only of Registered Medical Practitioners or a Hospital or a Laboratory
PRIORIX®
Measles, Mumps and Rubella Vaccine (live) IP
1.
NAME OF THE MEDICINAL PRODUCT
Measles, Mumps and Rubella Vaccine (live) IP
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each dose (0.5 ml) of the reconstituted vaccine contains:
Live attenuated measles virus (Schwarz strain) [propagated in chick embryo tissue cultures]:
≥103.0 CCID 50
Live attenuated mumps virus (RIT 4385 strain) [propagated in chick embryo tissue cultures]:
≥103.7 CCID 50
Live attenuated rubella virus (RA27/3 strain) [propagated in MRC5 human diploid cells]:
≥103.0 CCID 50
Neomycin Sulphate ≤25 mcg
Water for injection qs 0.5 ml
For a full list of excipients, see section 6.1 List of Excipients
PRIORIX is a lyophilised mixed preparation of the attenuated Schwarz measles, RIT 4385
mumps (derived from Jeryl Lynn strain) and Wistar RA 27/3 rubella strains of viruses,
separately obtained by propagation either in chick embryo tissue cultures (mumps and
measles) or MRC5 human diploid cells (rubella).
PRIORIX meets the World Health Organisation requirements for manufacture of biological
substances and for measles, mumps and rubella vaccines and combined vaccines (live).
3.
PHARMACEUTICAL FORM
Powder and solvent for solution for injection.
The lyophilized component of the measles, mumps and rubella viruses is a white to slightly
pink powder.
The solvent is a clear, colorless solution.
4.
Clinical particulars
4.1
Therapeutic indications
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PRIORIX is indicated for the active immunisation against measles, mumps and rubella.
4.2
Posology and method of administration
Posology
Use of PRIORIX should be based on official recommendations.
The dose is 0.5 ml. A second dose should be administered according to the official
recommendations.
PRIORIX can be used in subjects who have previously been vaccinated with another
monovalent or combined vaccine against measles, mumps and rubella.
Method of administration
PRIORIX is designed for subcutaneous injection although it can also be administered via
intramuscular injection (see section 4.4 Special warnings and precautions for use and 5.1
Pharmacodynamic properties).
The vaccine should preferably be administered subcutaneously to patients with
thrombocytopenia or a coagulation disorder (see section 4.4 Special warnings and
precautions for use).
For instructions on reconstitution of the medicinal product before administration, see section
6.6 Special precautions for disposal and other handling.
4.3
Contraindications
Hypersensitivity to the active substances or to one of the excipients cited in section 6.1 List of
excipients, or to neomycin. A history of contact dermatitis to neomycin is not a
contraindication. For hypersensitivity reactions related to egg proteins, see section 4.4 Special
warnings and precautions for use.
Cellular or humoral severe combined immunodeficiency (primary or acquired), for example
severe combined immunodeficiency, agammaglobulinemia and AIDS, or symptomatic
infection due to HIV or with an age-dependent level of CD4+ T lymphocytes in children less
than 12 months of age: CD4 + < 25%; children from 12 to 35 months of age; CD4 + < 20%:
children from 36 to 59 months of age; CD4 + < 15% (see section 4.4 Special warnings and
precautions for use.
Pregnancy. In addition, pregnancy should be avoided in the month following vaccination (see
section 4.6 Pregnancy and lactation).
As for other vaccines, administration of PRIORIX should be postponed in subjects with
severe febrile illnesses. A minor infection such as a cold should not delay vaccination.
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4.4
Special warnings and precautions for use
As with all injectable vaccines, appropriate medical treatment and supervision should always
be readily available in case of a rare anaphylactic event 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.
Infants below 12 months of age may not respond sufficiently to the measles component of the
vaccine, due to the possible persistence of maternal measles antibodies. This should not
preclude the use of the vaccine in younger infants (<12 months) since vaccination may be
indicated in some situations such as high-risk areas. In these circumstances revaccination at
or after 12 months of age should be considered (see section 5.1 Pharmacodynamic
properties).
PRIORIX should be administered with caution in persons with a Central Nervous System
(CNS) disorder, a predisposition to febrile convulsions or a family history of convulsions.
Vaccinees with a history of febrile convulsions should be monitored closely.
The measles and mumps components of the vaccine are produced in chick embryo cell
culture and may therefore contain traces of egg protein. Persons with a history of
anaphylactic, anaphylactoid, or other immediate allergic reactions (e.g. generalized urticaria,
swelling of the mouth and throat, difficulty breathing, hypotension, or shock) subsequent to
egg ingestion may be at an enhanced risk of immediate-type hypersensitivity reactions after
vaccination, although these types of reactions have been shown to be very rare. Individuals
who have experienced anaphylaxis after ingestion of eggs should be vaccinated with extreme
caution, with adequate treatment for anaphylaxis on hand should such a reaction occur.
Patients with a rare hereditary intolerance to fructose should not be vaccinated with
PRIORIX, as it contains sorbitol.
Limited protection from measles can be obtained by vaccination up to 72 hours after natural
exposure to the measles virus.
Syncope (fainting) can occur after, or even before, any vaccination, especially in adolescents.
This is a psychogenic response to the injection needle. This may be accompanied by several
neurological signs such as a transient disturbance in vision, paresthesia and tonicoclonic
movements of the limbs during recovery. It is important to establish procedures to avoid any
injury related to fainting.
As for any vaccine, a protective immune response may not be obtained in all vaccinees.
PRIORIX SHOULD UNDER
INTRAVASCULARLY.
NO
CIRCUMSTANCES
BE
ADMINISTERED
Thrombocytopenia
Cases of aggravation of thrombocytopenia and recurrence of thrombocytopenia in subjects
who have presented thrombocytopenia after the first dose have been reported after
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vaccination with live measles, mumps and rubella vaccines. Thrombocytopenia associated
with vaccination against measles, mumps and rubella is rare and generally resolves
spontaneously. In patients with thrombocytopenia or a history of thrombocytopenia after a
vaccination against measles, mumps or rubella, the benefit/risk ratio for administration of
PRIORIX should be evaluated carefully. These patients should be vaccinated with caution
and preferably subcutaneously.
Immunosuppressed patients
Vaccination can be considered for patients presenting some immune deficiencies in whom the
expected benefits are greater than the risks (for example, subjects infected by asymptomatic
HIV, IgG subclass deficiencies, congenital neutropenia, chronic granulomatous disease,
complement deficiencies).
Immunosuppressed patients who present no contraindication to this vaccination (see section
4.3 Contraindications) may not respond as well as immunocompetent subjects: some of these
patients may also be infected by the measles, mumps or rubella viruses in the event of
contact, despite appropriate vaccination. These patients should be monitored carefully for any
sign of measles, parotitis and rubella.
Transmission
Transmission of the measles and mumps viruses to non-immunized contact subjects by
vaccinees has never been documented. Pharyngeal excretion of the rubella and measles
viruses is known to occur in general between the 7th and 28th day after vaccination, with a
peak in excretion around the 11th day.
However, there is no proof of transmission of the excreted vaccine viruses to non-immunized
contact subjects. Transmission of the rubella vaccine virus to infants through breast milk or
transplacentally with no apparent clinical sign has been documented.
4.5
Interaction with other medicinal products and other forms of interaction
PRIORIX can be given simultaneously but at different injection sites with any of the
following monovalent or combination vaccines [including hexavalent vaccines (DTPa-HepBIPV/Hib)]: diphtheria-tetanus-acellular pertussis vaccine (DTPa), Haemophilus influenzae
type b vaccine (Hib), inactivated poliomyelitis vaccine (IPV), hepatitis B vaccine (HepB),
hepatitis A vaccine (HepA), meningococcal group C conjugate vaccine (MenC), varicella
vaccine (VZV), oral poliomyelitis vaccine (OPV) and 10-valent pneumococcal conjugate
vaccine, according to the official recommendations.
If administration is not simultaneous, an interval of at least one month between
administration of PRIORIX and other live attenuated vaccines is recommended.
There are no data on administration of PRIORIX with any other vaccine.
If tuberculin testing has to be done it should be carried out before or simultaneously with
vaccination, as it has been reported that measles, mumps and rubella vaccines can cause a
temporary reduction in tuberculin skin sensitivity. As this anergy may persist up to a
maximum of 6 weeks, tuberculin testing should not be conducted during this post-vaccination
period to avoid false negative results.
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In subjects who have received human gamma globulins or a blood transfusion, vaccination
should be postponed by 3 months or more (up to 11 months), depending on the dose of
human immunoglobulins administered, because of the risk of vaccine failure due to passively
acquired antibodies against measles, mumps and rubella.
4.6
Pregnancy and lactation
Fertility
PRIORIX has not been evaluated in fertility studies.
Pregnancy
Pregnant women should not be vaccinated with PRIORIX.
However, no harmful effect on the fetus has been documented after administration of
vaccines against measles, mumps or rubella to pregnant women.
Although a theoretical risk cannot be excluded, no case of congenital rubella syndrome has
been reported in over 3500 women who were in the initial stages of pregnancy without
knowing it at the time of administration of a rubella vaccine. Consequently, inadvertent
vaccination of pregnant women who are not aware of their pregnancy with the measles,
mumps and rubella vaccines should not be a reason for interruption of the pregnancy.
Pregnancy should be avoided in the month following vaccination. Women intending to
become pregnant should be advised to postpone their plans.
Lactation
There are limited data on PRIORIX during lactation. Studies have shown that women
breastfeeding postpartum and vaccinated with live attenuated rubella vaccines can excrete the
virus in breast milk and transmit it to the breastfed enfant with no apparent clinical symptom.
Only if is confirmed or suspected that the child is immune-deficient should the benefit/risk
ratio of vaccination of the mother be evaluated (see section 4.3 Contraindications).
4.7
Effects on ability to drive and use machines
PRIORIX has no effect or a negligible effect on the ability to drive vehicles and use
machines.
4.8
Undesirable effects
Summary of the tolerance profile
The tolerance profile described below is based on a total of approximately 12,000 subjects
vaccinated with PRIORIX in clinical trials.
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The undesirable effects that can occur after use of the measles, mumps and rubella combined
vaccine correspond to those observed after administration of the monovalent vaccines alone
or in combination.
In controlled clinical trials, signs and symptoms were actively monitored over a follow-up
period of 42 days. Vaccinees were also requested to report any clinical event during the study
period.
The most common undesirable effects following administration of PRIORIX were redness at
the injection site and fever ≥38°C (rectal) or ≥37.5°C (axillary/oral).
List of undesirable effects
Undesirable effects are listed according to the following frequencies:
Very common:
(≥1/10)
Common:
(≥1/100 to <1/10)
Uncommon:
(≥1/1,000 to <1/100)
Rare:
(≥1/10,000 to <1/1,000)
Data from clinical studies
Infections and infestations
Common: upper respiratory tract infection
Uncommon: otitis media
Blood and lymphatic system disorders
Uncommon: Iymphadenopathy
Immune system disorders
Rare: Allergic reactions
Metabolism and nutrition disorders
Uncommon: anorexia
Psychiatric disorders:
Uncommon: nervousness, abnormal crying, insomnia
Nervous system disorders:
Rare: febrile convulsions
Eye disorders
Uncommon: conjunctivitis
Respiratory, thoracic and mediastinal disorders
Uncommon: bronchitis, cough
Gastrointestinal disorders:
Uncommon: parotitis, diarrhea, vomiting
Skin and subcutaneous tissue disorders
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Common: rash
General disorders and administration site conditions:
Very common: erythema at the injection site, fever ≥38°C (rectal) or ≥37.5 °C (axillary/oral)
Common: pain and swelling at the injection site, fever >39.5°C (rectal) or >39°C
(axillary/oral)
In general, the frequency of undesirable reactions was similar after the first and second dose
of the vaccine, with the exception of the pain at the injection site, which was reported to be
'"common" after the first dose, and "very common" after the second dose
Post-marketing surveillance data
During post-marketing surveillance, the following undesirable effects were reported
following vaccination with PRIORIX.
As these effects were reported spontaneously, it is not possible to reliably estimate their
frequency.
Infections and infestations
Meningitis, orchitis, epididymitis, mild or attenuated atypical measles, syndrome resembling
mumps.
Blood and lymphatic system disorders
Thrombocytopenia, thrombocytopenic purpura
Immune system disorders
Anaphylactic reactions
Nervous system disorders:
Transverse myelitis, Guillain Barré syndrome, peripheral neuritis, encephalitis*
Skin and subcutaneous tissue disorders
Erythema multiform
Musculoskeletal and connective tissue disorders:
Arthralgia, arthritis
General disorders and administration site conditions:
Kawasaki syndrome
*Encephalitis was reported at a frequency of 1 per 10 million doses. The risk of encephalitis
after administration of the vaccine is far lower than the risk of encephalitis caused by natural
disease (measles: 1 in 1000 to 2000 cases, mumps: 2-4 in 1000 cases, rubella: approximately
1 in 6000 cases).
Accidental intravascular administration can lead to severe reactions or even to shock.
Immediate measures depend on the severity of the reaction (see section 4.4 Special warnings
and precautions for use).
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4.9
Overdose
Cases of overdose (up to 2 times the recommended dose) were reported during the postmarketing monitoring. No secondary effects were associated with this overdose.
5.
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: Viral vaccine, ATC code J07BD52
Immune response in children 12 months of age and over
In clinical studies conducted with children from 12 months to 2 years of age, PRIORIX
showed high immunogenicity.
Vaccination with a single dose of PRIORIX induces the production of antibodies against
measles, mumps and rubella in 98.1 %, 94.4% and 100% respectively of initially
seronegative subjects.
Two years after the initial vaccination, the seroconversion rates were 93.4 % for measles,
94.4% for mumps and 100% for rubella.
Although no data are available on the protective efficacy of PRIORIX, immunogenicity is
considered an indication of protective efficacy. However, some field studies have reported
that the protective efficacy against mumps could be lower than the observed seroconversion
rates for this disease.
Immune response in infants from 9 to 10 months of age
A clinical trial enrolled 300 healthy infants 9 to 10 months of age at the time of first vaccine
dose. Of these, 147 subjects received PRIORIX and VARILRIX simultaneously. The
seroconversion rates for measles, mumps and rubella were 92.6%, 91.5% and 100%
respectively. The seroconversion rates reported after the second dose of vaccination
administered 3 months after the first dose were 100% for measles, 99.2% for mumps and
100% for rubella. It appears therefore that a second dose of PRIORIX should be administered
in the 3 months following the first dose to obtain optimal immune responses.
Adolescents and adults
The safety and immunogenicity of PRIORIX in adolescents and adults have not been
specifically studied in clinical trials.
Intramuscular administration
A limited number of subjects received PRIORIX intramuscularly in the course of the clinical
trials. The seroconversion rates for the three valences of the vaccine were comparable to
those obtained after subcutaneous administration.
5.2
Pharmacokinetic properties
Pharmacokinetic studies are not necessary for vaccines.
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5.3
Preclinical safety data
Nonclinical data from conventional safety studies have not shown any particular risk for
humans.
6.
6.1
PHARMACEUTICAL PARTICULARS
List of excipients
Vaccine: Amino acids, lactose, mannitol, neomycin sulphate, sorbitol.
Diluent: Water for injection.
6.2
Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other
medicinal products.
6.3
Shelf life
24 months
The vaccine should be injected immediately after reconstitution. If this is not possible, it
should be stored between + 2°C and + 8°C and used within 8 hours following reconstitution.
6.4
Special precautions for storage
Store and transport refrigerated (between 2°C and 8°C).
Do not freeze.
Store in the original packaging, protected from light.
For storage conditions for the medicinal product after reconstitution, see section 6.3 Shelf life.
Keep out of reach of children
6.5
Nature and contents of container
Powder in a vial (type I glass) sealed by a rubber stopper.
0.5 ml of solvent in a pre-filled syringe (type I glass) equipped with a piston stopper (rubber)
with or without separate needles.
OR
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0.5 ml of solvent in an ampoule (type I glass)
Pack sizes of 1, 10 or 100
Not all pack sizes may be marketed.
6.6
Special precautions for disposal and other handling
The solvent and the reconstituted vaccine should be inspected visually for any foreign
particulate matter and/or abnormal physical appearance before administration. If either is
observed, the vaccine should be discarded.
The vaccine should be reconstituted by adding the entire contents of the pre-filled syringe /
ampoule of solvent provided to the vial containing the powder.
Instructions on use of the pre-filled syringe
To attach the needle to the syringe, refer to the illustration below. Note however that the
syringe provided with PRIORIX may differ slightly (without threading) from the syringe
shown.
In this case, the needle should not be screwed into the syringe to attach it.
Needle
Needle protector
Syringe
Syringe plunger
Syringe barrel
Syringe cap
1. Hold the barrel of the syringe with one hand (avoid holding the syringe by the plunger),
and unscrew the cap from the syringe by turning it counterclockwise.
2. To attach the needle to the syringe, turn the needle clockwise to insert it into the syringe
until it locks (see illustration).
3. Remove the needle protector, which can sometimes be slightly stiff, from the needle.
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.
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The colour of the reconstituted vaccine may vary from clear peach to fuchsia pink due to
minor variations of its pH. This is normal and does not impair the performance of the
vaccine. In the event of other variation being observed, discard the vaccine.
A new needle should be used to administer the vaccine.
Inject the entire contents of the vial.
Contact with disinfectants should be avoided (see section 4.4 Special warnings and
precautions for use).
Any unused medicinal product or waste material should be disposed of in accordance with
local requirements.
7.
MARKETING AUTHORISATION HOLDER
GlaxoSmithKline Asia Private Limited
Registered Office:
Patiala Road,
Nabha (Punjab) 147 201
8.
MARKETING AUTHORISATION NUMBER(S)
Not applicable
9.
DATE
OF
AUTHORISATION
FIRST
AUTHORISATION/RENEWAL
OF
Date of first authorization: 24th March 1999
Manufactured by:
Fidia Farmaceutici S.P.A at Via
Ponte della Fabrica 3/A, 35031Abano Terme (PD), Italy
Labelled / Packed by:
GlaxoSmithKline Asia Pvt Ltd.,
A-10/1, MIDC, Ambad,
Nashik 422010
Testing and Release by:
GlaxoSmithKline Biologicals
s.a.
Rue de l’Institut, 89
B-1330 Rixensart, Belgium.
For further information please
contact:
GlaxoSmithKline
Pharmaceuticals Limited,
Registered office:
Dr. Annie Besant Road, Worli
Mumbai 400 030, India
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Imported by:
GlaxoSmithKline Asia Pvt Ltd.,
North Eastern Side of Ground
Floor of Building No. 144
Poonamallee High Road,
Vellappanchavadi,
Chennai-77
THE
PRIORIX and VARILRIX are registered trademarks of GlaxoSmithKline.
PRX-N /PI/IN/2014/02 dated 15th May, 2014
Adapted from Belgian SPC approved 9th August, 2013 [GDS 12 dated 24th October, 2012]
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