Active ingredients: Vaccine (live) anti-measles, anti-mumps, anti-rubella and anti-varicella
Priorix Tetra, powder and solvent for solution for injection in pre-filled syringe
Indications Why is Priorix tetra used? What is it for?
Priorix Tetra is a vaccine, used in children from 11 months up to and including 12 years of age, for the prevention of diseases caused by the measles, mumps, rubella and chicken pox viruses.
In some situations Priorix Tetra can also be given to babies from 9 months of age.
How Priorix Tetra works
When a person is vaccinated with Priorix Tetra, their immune system (the body's natural defense system) develops antibodies that protect them from infection with measles, mumps, rubella and chicken pox viruses.
Although Priorix Tetra contains live viruses, they are too weak to cause measles, mumps, rubella or chickenpox in healthy people.
Like all vaccines, Priorix Tetra may not fully protect all vaccinated people.
Contraindications When Priorix tetra should not be used
Do not use Priorix Tetra:
- if your child is allergic to even one of the ingredients of this vaccine (listed in section 6). Signs of an allergic reaction may include itchy rash, feeling short of breath, swelling of the face or tongue;
- if your child has previously had an allergic reaction to any measles, mumps, rubella and / or chicken pox vaccine;
- if your child has had an allergy to neomycin (an antibiotic agent). A known contact dermatitis (skin rash that appears when the skin is in direct contact with allergens such as neomycin) is not a problem but must first be reported to the doctor;
- if your child has a "severe infection with a high temperature. In these cases, vaccination should be postponed until recovery. A" mild infection such as a cold is not a problem, but you must first report this to your doctor;
- if your child has any disease (such as Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS)) or is taking medicines that can weaken the immune system. The choice of whether or not to give the vaccine to your child will depend from the level of the immune defenses.
- In case of pregnancy. Furthermore, pregnancy should be avoided in the first month following vaccination.
Precautions for use What you need to know before taking Priorix tetra
Talk to a doctor or pharmacist before your child receives Priorix Tetra if:
- your child has a personal or family history of seizures including febrile seizures. In this case, your child must be closely monitored after vaccination as fever may occur particularly 5 to 12 days after vaccination (see also section 4);
- your baby has had a severe allergic reaction to egg proteins;
- your child has developed side effects after a measles, mumps or rubella vaccination which resulted in more prolonged bruising or bleeding easily (see also section 4);
- if your child has a weakened immune system (for example, due to an "HIV infection). Your child should be closely monitored as the response to the vaccine may not be sufficient to provide protection against the disease (see Section 2 "Do not use Priorix Tetra").
If your baby is vaccinated within 72 hours of contacting someone with measles or chickenpox, Priorix Tetra can partially protect your baby from the disease.
Once vaccinated, your child should try to avoid close contact with the following individuals as much as possible for at least 6 weeks after vaccination:
- individuals with reduced disease resistance,
- pregnant women who have not had chickenpox or who have not been vaccinated against chickenpox.
- infants from mothers who have not had chickenpox or who have not been vaccinated against chickenpox.
Fainting may occur (especially in adolescents) following, or even before, any needle injection. Therefore tell your doctor or nurse if your child has passed out with a previous injection.
Like other vaccines, Priorix Tetra may not fully protect your baby against chickenpox. However, people who have been vaccinated and who have contracted chickenpox usually have very mild disease when compared to people who have not been vaccinated.
Interactions Which drugs or foods may change the effect of Priorix tetra
Tell your doctor if your child is taking, has recently taken or might take any other medicines or has recently received any other vaccine.
If your baby has had a transfusion of blood or human antibodies (immunoglobulins) your doctor will postpone the vaccination for at least 3 months.
If your child has to have a tuberculin test, this should be done before, at the same time or 6 weeks after vaccination with Priorix Tetra.
The use of salicylates (a substance found in many medicines used to lower fever and relieve pain) should be avoided for 6 weeks following vaccination with Priorix Tetra.
Priorix Tetra can be given at the same time as other vaccines. A different injection site should be used for each vaccine.
Warnings It is important to know that:
Pregnancy and breastfeeding
Priorix Tetra should not be given to pregnant women. If you are pregnant, think you may be pregnant or are planning to have a baby, or if you are breast-feeding, ask your doctor or pharmacist for advice before receiving this vaccine. In addition, it is important to avoid becoming pregnant in the first month after vaccination. During this time, an effective method of contraception should be used to avoid pregnancy.
Priorix Tetra contains sorbitol
If your child has been diagnosed with "intolerance to some sugars, contact your doctor before your child receives the vaccination."
Dose, Method and Time of Administration How to use Priorix tetra: Posology
Priorix Tetra is administered subcutaneously in the upper arm or outer thigh.
Priorix Tetra is intended for children aged 11 months to 12 years inclusive. Your doctor will determine the timing and number of injections to give to your child based on official recommendations.
The vaccine should never be administered intravenously.
Side Effects What are the side effects of Priorix tetra
Like all medicines, this vaccine can cause side effects, although not everybody gets them. The following side effects can occur with this vaccine:
Very common (these may occur in more than 1 in 10 doses of the vaccine):
- pain and redness at the injection site
- fever of 38 ° C or higher *
Common (these may occur in up to 1 in 10 doses of the vaccine):
- swelling at the injection site
- fever higher than 39.5 ° C *
- irritability
- rash (spots and / or blisters)
Uncommon (these may occur in up to 1 in 100 vaccine doses):
- unusual crying, nervousness, inability to sleep
- general malaise, drowsiness, fatigue
- swelling of the parotid glands (glands found in the cheek)
- diarrhea, vomiting
- loss of appetite
- upper respiratory tract infection
- rhinitis
- swelling of the lymph glands
Rare (these may occur in up to 1 in 1,000 doses of the vaccine):
- middle ear infections
- febrile seizures
- cough
- bronchitis
* Higher rates of fever were observed after administration of the first dose of Priorix Tetra compared to mumps-measles-rubella and varicella vaccines given separately at the same visit.
On a few occasions the following adverse reactions have been reported during routine use of GlaxoSmithKline Biologicals vaccines against measles, mumps, rubella or varicella:
- Pain in the joints and muscles
- Allergic reactions. Skin rashes that may itch or blister, swelling of the eyes and face, difficulty in breathing or swallowing, sudden drop in blood pressure and loss of consciousness. These reactions may occur before you leave the doctor's office. In any case, if your child has any of these symptoms, contact a doctor immediately.
- Infection or inflammation of the brain, spinal cord and peripheral nerves resulting in temporary difficulty when walking (instability) and / or temporary loss of control of body movements, stroke, inflammation of certain nerves, possibly with tingling or loss of sensation or normal movements (Guillain-Barré syndrome)
- Narrowing or blockage of blood vessels
- Point or spot bleeding, or bruising more frequently than normal due to a decrease in platelets
- Erythema multiforme (symptoms of which are red, often itchy, rash-like spots from measles that begin in the limbs and sometimes the face and rest of the body)
- Chickenpox-like rash
- St. Anthony's Fire (herpes zoster)
- Symptoms similar to measles and mumps (including painful transient swelling of the testicles and swollen glands in the neck)
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this vaccine out of the sight and reach of children.
Do not use this vaccine after the expiry date which is stated on the package. The expiry date refers to the last day of the month.
Store and transport refrigerated (2 ° C - 8 ° C).
Do not freeze.
Store in the original package to keep it away from light.
After reconstitution, the vaccine should be administered immediately or stored in a refrigerator (2 ° C - 8 ° C). If it is not used within 24 hours, it must be discarded.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines your child no longer uses. This will help protect the environment.
Other information
What Priorix Tetra contains
- The active ingredients are: live attenuated measles, mumps, rubella and chicken pox viruses.
- The other ingredients are: Powder: amino acids, anhydrous lactose, mannitol, sorbitol, medium 199 Solvent: water for injections.
Description of Priorix Tetra appearance and contents of the package
Priorix Tetra is presented as a powder and solvent for solution for injection (powder in a 1 dose vial and solvent in a pre-filled syringe (0.5 ml)) with or without separate needles, in the following pack sizes:
- with 2 separate needles: packs of 1 or 10 doses.
- without needles: packs of 1, 10, 20 or 50 doses.
Priorix Tetra is presented as a white to pale pink powder and a clear colorless solvent (water for injections) for reconstitution of the vaccine.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
PRIORIX TETRA - POWDER AND SOLVENT FOR SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
VACCINE (ALIVE) ANTI-WORBILL, ANTI-PAROTITIS, ANTIROSOLIA AND ANTIVARICELLA
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
After reconstitution, 1 dose (0.5 ml) contains:
measles virus1 Schwarz strain (live, attenuated) not less than 103.0 CCID503
mumps virus1 strain RIT 4385, derived from Jeryl Lynn strain (live, attenuated)
not less than 104.4 CCID503
rubella virus2 Wistar RA 27/3 strain (live, attenuated) not less than 103.0 CCID503
varicella virus2 OKA strain (live, attenuated) not less than 103.3 PFU4
1 cultured in chicken embryonic cell cultures
2 cultured in human diploid cells (MRC-5)
3 Cell Culture Infective Dose 50% 4 Plaque Forming Units
This vaccine contains traces of neomycin. See section 4.3.
Excipient with known effect:
The vaccine contains 14 mg of sorbitol, see section 4.4.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Powder and solvent for solution for injection in pre-filled syringe.
Before reconstitution, the powder is a white to light pink tablet and the solvent is a clear, colorless liquid.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Priorix Tetra is indicated for active immunization against measles, mumps, rubella and chickenpox in children from 11 months up to and including 12 years of age.
Administration to children of 9 - 10 months may be considered in special circumstances. See section 4.2
Note: Priorix Tetra should be used according to official recommendations.
04.2 Posology and method of administration
Dosage
Children from 11 months to 12 years old
Infants and children aged 11 months to 12 years should receive two doses (0.5 ml each) of Priorix Tetra. The age at which infants or children can receive Priorix Tetra should be based on official recommendations *, which vary according to the epidemiology of these diseases.
The interval between doses should preferably * be between 6 weeks and 3 months. When the first dose is given at 11 months of age, the second dose should be given within 3 months. In no case is the interval between doses must be less than 4 weeks. See section 5.1.
Alternatively, and in accordance with official recommendations *:
- A single dose of Priorix Tetra may be given to children who have already received immunization with a single dose of another measles, mumps and rubella (MMR) vaccine and / or a single dose of another vaccine against chickenpox.
- A single dose of Priorix Tetra may be followed by a single dose of another measles, mumps and rubella (MMR) vaccine and / or a single dose of another varicella vaccine.
* Official recommendations may vary with respect to the interval between doses and the need to administer one or two doses of vaccine containing measles, mumps, rubella and vaccine containing varicella.
Babies from 9 to 10 months
If a particular epidemiological situation requires vaccination of individuals under the age of 11 months, the first dose of Priorix Tetra can be administered from 9 months of age. A second dose should be administered 3 months after the first dose (see section 5.1).
Method of administration
The vaccine should be injected subcutaneously, in the deltoid region of the arm or in the upper anterolateral part of the thigh.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
04.3 Contraindications
As with other vaccines, administration of Priorix Tetra should be postponed in subjects suffering from acute severe febrile illness. However, the presence of a "mild infection, such as a cold, should not lead to a postponement of vaccination.
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or to neomycin. A history of neomycin contact dermatitis is not a contraindication. For egg allergy, see section 4.4.
Hypersensitivity after previous administration of measles, mumps, rubella and / or chicken pox vaccines.
Severe humoral or cellular immunodeficiency (primary or acquired), for example severe combined immunodeficiency, agammaglobulinemia and AIDS or symptomatic HIV infection, or an age-specific percentage of CD4 + T cells in infants less than 12 months of age: CD4 +
Pregnancy. Furthermore, pregnancy should be avoided in the first month following vaccination (see section 4.6).
04.4 Special warnings and appropriate precautions for use
As with all injectable vaccines, appropriate treatment and medical supervision should always be readily available in case of rare anaphylactic reactions following the administration of the vaccine.
Alcohol and other disinfecting agents should be allowed to evaporate from the skin before injecting the vaccine, as these can inactivate the attenuated viruses present in the vaccine.
The components of the measles and mumps vaccine are produced in chicken embryonic cell cultures and may therefore contain traces of egg protein. Individuals with a history of anaphylactic, anaphylactoid, or other immediate reactions (eg generalized urticaria) , swelling in the mouth and throat, difficulty breathing, hypotension or shock) following egg ingestion, may be at increased risk of developing immediate hypersensitivity reactions following vaccination, although these types of reactions have occurred very rarely . Individuals who have developed anaphylaxis after ingestion of eggs should be vaccinated with extreme caution, taking care to have adequate treatment available for anaphylaxis should such a reaction occur.
Individuals with rare hereditary problems of fructose intolerance should not receive this vaccine.
Salicylates should be avoided for 6 weeks after each vaccination with Priorix Tetra, as cases of Reye's syndrome have been reported after the use of salicylates during natural chickenpox infection.
Limited protection against measles or chickenpox can be achieved with vaccination within 72 hours of exposure to the natural disease.
Febrile seizures
An increased risk of fever and febrile seizures was observed 5 to 12 days after the first dose of Priorix Tetra compared to concomitant administration of MMR vaccine and varicella vaccine (see sections 4.8 and 5.1).
Vaccination of individuals with a personal or family history of seizures (including febrile seizures) should be considered with caution. For these subjects, an alternative immunization for the first dose with separate MMR and varicella vaccines should be considered (see section 4.2). In any case, vaccinates should be checked for fever during the risk period.
Fever is usually elevated after the first dose of measles virus vaccines. There were no indications of an increased risk of fever after the second dose.
Immunocompromised patients
Vaccination may be considered in patients with selected immunodeficiencies where the benefits outweigh the risks (e.g. patients with asymptomatic HIV, IgG subclass deficiencies, congenital neutropenia, chronic granulomatous disease, and complement deficiency disorders).
Immunocompromised patients who have no contraindication for this vaccination (see section 4.3) may not respond as well as immunocompetent patients; therefore, some of these patients may contract measles, mumps, rubella or chickenpox upon contact, despite "appropriate vaccine administration. These patients should be closely monitored for symptoms of measles, mumps, rubella and chicken pox. .
Transmission
The transmission of measles, mumps and rubella viruses from vaccinated to susceptible people who have come into contact with them has never been documented, although pharyngeal excretion of rubella virus is known to occur 7 to 28 days after vaccination. , with a peak of excretion around the 11th day.
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 virus from a vaccinee who has not developed rash on seronegative contacts cannot be excluded. Vaccinated individuals, including those who do not develop a chickenpox-like rash, should try to avoid, as far as possible, close contact with high-risk individuals susceptible to chickenpox for at least 6 weeks after vaccination. In cases where contact with high-risk individuals susceptible to chickenpox is unavoidable, the potential risk of transmission of the varicella vaccine virus should be weighed against the risk of acquiring and transmitting wild varicella virus.
High-risk individuals susceptible to chickenpox include:
• Immunocompromised individuals (see sections 4.3 and 4.4)
• Pregnant women without a documented "history of chickenpox or" laboratory evidence of previous infection.
• Infants from mothers without a documented "history of chickenpox or" laboratory evidence of previous infection.
Priorix Tetra must under no circumstances be administered intravascularly or intradermally.
Thrombocytopenia
There have been reports of worsening of thrombocytopenia and cases of recurrence of thrombocytopenia in subjects suffering from thrombocytopenia after the first dose following vaccination with live measles, mumps and rubella vaccines. In these cases, the risk-benefit balance of immunization with Priorix Tetra must be carefully considered.
Syncope (fainting) may occur following, or even before, any vaccination especially in adolescents as a psychogenic response to needle injection. It may be accompanied by various neurological signs such as transient visual disturbances, paraesthesia and tonic-clonic movements of the limbs. during the recovery phase It is important that adequate procedures are in place to avoid injury resulting from fainting.
As with all vaccines, not all vaccinates may get a protective immune response. As with other chickenpox vaccines, cases of chickenpox disease have been shown to have occurred in people who had previously received Priorix Tetra. These sporadic cases are usually mild, with fewer lesions and lower fever than in unvaccinated individuals.
There are very few reports of disseminated chickenpox with internal organ involvement following vaccination with varicella Oka strain vaccines mainly in immunocompromised individuals.
Interference with serological testing (see section 4.5)
04.5 Interactions with other medicinal products and other forms of interaction
Clinical studies have shown that Priorix Tetra can be administered concurrently with any of the following monovalent or combination vaccines [including hexavalent vaccines (DTPa-HBV-IPV / Hib)]: diphtheria vaccine, tetanus, acellular pertussis (DTPa), vaccine against L"Haemophilus influenzae type b (Hib), inactivated polio vaccine (IPV), hepatitis B (HBV) vaccine, meningococcal serogroup B (Men B) vaccine, meningococcal conjugate serogroup C (Men C) vaccine, meningococcal conjugate serogroup A , C, W-135 and Y (MenACWY) and pneumococcal 10-valent conjugate vaccine.
Due to an increased risk of fever, injection site tenderness, change in eating habits and irritability when Bexsero was co-administered with Priorix Tetra, separate vaccinations may be considered whenever possible.
There is currently insufficient data to support the use of Priorix Tetra with any other vaccine.
If Priorix Tetra is to be administered at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.
Serological tests
If tuberculin testing is to be performed, it should be performed before or at the same time as vaccination, as combined measles, mumps and rubella vaccines have been reported to cause a temporary reduction in skin sensitivity to tuberculin. As this anergy can last up to a maximum of 6 weeks, the tuberculin test should not be performed within this period after vaccination to avoid false negatives.
In individuals who have received human gamma globulin or blood transfusions, vaccination should be delayed for at least three months due to the likelihood of vaccination failure due to the presence of passively acquired antibodies.
Subjects receiving the vaccine should avoid the use of salicylates for 6 weeks after each vaccination with Priorix Tetra (see section 4.4).
04.6 Pregnancy and breastfeeding
Fertility
Priorix Tetra has not been evaluated in fertility studies.
Pregnancy
Pregnant women should not be vaccinated with Priorix Tetra.
However, no fetal harm has been documented following the administration of measles, mumps, rubella or chicken pox vaccines to pregnant women.
Pregnancy should be avoided in the first month following vaccination. It is therefore necessary to advise women who intend to become pregnant to postpone it.
Breastfeeding
There are no adequate human data on the use of Priorix Tetra during lactation.
04.7 Effects on ability to drive and use machines
Not relevant.
04.8 Undesirable effects
Summary of the safety profile
The safety profile presented below is based on data from clinical studies in which over 6,700 doses of Priorix Tetra were administered to more than 4,000 children aged 9 to 27 months. Events were recorded for up to 42 days after vaccination.
The most common adverse reactions following administration of Priorix Tetra were pain and redness at the injection site and fever ≥ 38 ° C (rectal) or ≥ 37.5 ° C (axillary / oral).
List of adverse reactions
Adverse reactions reported are listed based on the following frequencies:
Very common (≥1 / 10)
Common (≥1 / 100 to
Uncommon (≥1 / 1,000 to
Rare (≥1 / 10,000 to
Very rare (
Data from clinical studies
Infections and infestations
Uncommon: upper respiratory tract infection
Rare: otitis media
Disorders of the blood and lymphatic system
Uncommon: lymphadenopathy
Metabolism and nutrition disorders
Uncommon: anorexia
Psychiatric disorders
Common: irritability
Uncommon: crying, nervousness, insomnia
Nervous system disorders
Rare: febrile convulsions *
Respiratory, thoracic and mediastinal disorders
Uncommon: rhinitis
Rare: cough, bronchitis
Gastrointestinal disorders
Uncommon: swelling of the parotid glands, diarrhea, vomiting
Skin and subcutaneous tissue disorders
Common: skin rash
General disorders and administration site conditions
Very common: injection site pain and redness, fever (rectal ≥ 38 ° C to ≤ 39.5 ° C; axillary / oral ≥ 37.5 ° C to ≤ 39 ° C) **
Common: injection site swelling, fever (rectal> 39.5 ° C; axillary / oral> 39 ° C) **
Uncommon: lethargy, malaise, fatigue
* The risk of febrile seizures in children aged 9-30 months following the first dose of Priorix Tetra vaccine was evaluated in a "retrospective database analysis compared to an MMR vaccine or simultaneous but separate administration of MMR vaccine." and chickenpox vaccine.
The study included 82,656 children immunized with MMRV, 149,259 with MMR, and 39,203 with separate MMR and varicella vaccines.
Depending on the case definition used to identify febrile seizures in the main risk period between 5 and 12 days after the first dose, the incidence of febrile seizures was 2.18 (95% CI: 1.38; 3 , 45) or 6.19 (95% CI: 4.71, 8.13) per 10,000 subjects for the MMRV group and 0.49 (95% CI: 0.19, 1.25) or 2, 55 (95% CI: 1.67, 3.89) per 10,000 subjects for the corresponding control cohorts.
These data suggest an additional case of febrile seizures for 5,882 or 2,747 subjects vaccinated with Priorix Tetra compared to matched control cohorts who received MMR or simultaneous but separate vaccination with MMR and varicella vaccine (attributable risk of 1.70 (95% CI: -1.86, 3.46) and 3.64 (95% CI: -6.11, 8.30) per 10,000 subjects, respectively) - see section 5.1.
** Following the administration of the first dose of the combined measles-mumps-rubella-varicella vaccine, a "higher incidence of fever (approximately 1.5 times) was observed compared to concomitant administration of measles-mumps-rubella and varicella vaccines. at different injection sites.
Post marketing surveillance data
The following additional adverse reactions have been identified on rare occasions during post marketing surveillance. As these were reported voluntarily from a population of unknown magnitude, it is not possible to provide a correct estimate of the frequency.
Infections and infestations
Meningitis, herpes zoster ***, measles-like syndrome, mumps-like syndrome (including orchitis, epididymitis and mumps)
Disorders of the blood and lymphatic system
Thrombocytopenia, thrombocytopenic purpura
Disorders of the immune system
Allergic reactions (including anaphylactic and anaphylactoid reactions)
Nervous system disorders
Encephalitis, cerebellitis, cerebrovascular accident, Guillain Barrè syndrome, transverse myelitis, peripheral neuritis, symptoms similar to those of cerebellitis (including transient gait disturbances and transient ataxia).
Vascular pathologies
Vasculitis
Skin and subcutaneous tissue disorders
Erythema multiforme, rash similar to chickenpox
Musculoskeletal and connective tissue disorders
Arthralgia, arthritis
*** This adverse drug reaction, reported after vaccination, is also a consequence of infection with wild varicella virus. There is no indication of an increased risk of getting herpes zoster following vaccination compared to that following wild virus disease.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
No cases of overdose have been reported.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmaco-therapeutic category: viral vaccine.
ATC code J07BD54.
Effectiveness
The efficacy of GlaxoSmithKline (GSK) monovalent Oka / RIT (Varilrix) and Priorix Tetra vaccines in varicella prevention was evaluated in a large randomized clinical trial, which included GSK's combined measles-mumps-rubella (Priorix) vaccine. as an active control. The study was conducted in Europe where a routine vaccination for chickenpox is not implemented. Children aged 12 to 22 months received two doses of Priorix Tetra six weeks apart. other (N = 2,279) or a dose of Varilrix (N = 2,263) and were followed for approximately 35 months after vaccination (long-term follow-up of 10 years is ongoing). The observed efficacy of varicella vaccine of any severity (defined using a prespecified scale) confirmed epidemiologically or by PCR (Polymerase Chaine Reactions) was 94.9% (97.5% CI: 92.4; 96.6%) after two doses Priorix Tetra and 65.4% (97.5% CI: 57 ,2; 72.1%) after a dose of Varilrix. The efficacy of confirmed, moderate or severe varicella vaccine 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 conducted in Finland specifically designed to evaluate the vaccine efficacy of Varilrix, 493 children between 10 and 30 months of age were monitored for a period of approximately 2.5 years after vaccination at one dose. The protective efficacy was 100% (95% CI: 80; 100%) against common or severe clinical cases of chickenpox (≥ 30 vesicles) and 88% (95% CI: 72; 96%) against any case confirmed serologically of chickenpox (at least 1 vesicle or papule).
Efficacy (post-marketing)
Post-marketing efficacy data suggest a higher level of protection and decreased onset of varicella following administration of two doses of varicella vaccine compared to a single dose.
The efficacy of two doses of Priorix Tetra during outbreaks of chickenpox in outpatient centers in Germany, where vaccination against chickenpox is routinely recommended for children as young as 11 months of age, was 91% (95% CI: 65; 98%) for chickenpox of any severity and 94% (95% CI: 54; 99%) for moderate disease.
The efficacy of one dose of Varilrix was estimated in different situations (epidemic, case control and database studies) and ranged from 20% to 92% against any grade of varicella and from 86% to 100% against moderate disease. or severe.
Immune response
Several clinical studies have evaluated the immune response induced by Priorix Tetra. The titration of antibodies against measles, mumps and rubella was determined using the commercially available ELISA (Enzyme Linked Immunosorbent Assay) method. In addition, antibodies to mumps were titrated using the plaque reduction neutralization test. These serological parameters are widely accepted as surrogate markers of immune protection. A modified commercial, indirect immunofluorescence (IFA) test and a commercial ELISA test, were employed to compare the immune response against varicella induced by Priorix Tetra with the immune response induced by the GSK vaccine.
In three clinical studies conducted in Europe (Austria, Finland, Germany, Greece, Poland), approximately 2,000 previously unvaccinated children between 11 and 23 months of age received two doses of Priorix Tetra with an interval between the two doses of 6 weeks. Seroconversion rates (SC) and geometric means of antibody concentrations / titers (GMC / GMT) are summarized in the table below.
Seroconversion rates and geometric means of antibody concentrations / titers were similar to those observed after separate vaccination with Varilrix and Priorix.
In infants vaccinated at 11 months of age, the proportion of infants with a protective titer against measles (i.e.> 150 mIU / mL) after the first dose is 91-92%, and is lower than the proportion observed when the first dose is administered from 12 months of age.
The second dose of Priorix Tetra resulted in an increase in seroconversion rates and / or levels of antibodies to the measles, mumps and rubella components of the vaccine. Therefore, to avoid infections during the interval between the two doses, it is preferable to administer the second dose within three months of the first.
The data suggest "higher efficacy and decreased appearance of chickenpox following two doses of the vaccine compared to a single dose. This correlates with an increase in varicella antibodies induced by the second dose, suggesting that the second dose dose of chickenpox antigen acts as a booster.
The immune response of Priorix Tetra administered as a second dose of MMR vaccine in children aged 24 months to 6 years was evaluated in 2 clinical studies. Children were previously vaccinated with a first dose of MMR vaccine or with an MMR vaccine co-administered with a live attenuated varicella vaccine, respectively. The seropositivity rates for varicella antibodies were 98.1% (IFA) in children previously vaccinated with MMR and 100% in children previously vaccinated with an MMR vaccine co-administered with a live attenuated varicella vaccine. Seropositivity rates were 100% for measles, mumps, and rubella antibodies in both studies.
Immune response in children between the ages of 9 and 10 months
A clinical study conducted in Asia (Singapore) enrolled 300 healthy children between the ages of 9 and 10 months at the time of the first vaccine dose. Of these, 153 subjects received two doses of Priorix Tetra with an interval between doses. 3 months and 147 subjects received Priorix and Varilrix. Seroconversion rates and geometric means of antibody concentrations / titers were similar to those observed after separate vaccination with Varilrix and Priorix. Seroconversion rates after a first dose of Priorix Tetra were comparable for all antigens, excluding measles antigens, to those found in infants aged 12 to 24 months from other clinical studies. The reported seroconversion rate for measles in subjects 9 to 10 months of age following the first dose of Priorix Tetra was 93.3% (95% CI: 87.6; 96.9). Children in their first year of life may not respond adequately to components i of the vaccine due to possible interference with maternal antibodies. Therefore, a second dose of Priorix Tetra should be administered three months after the first dose.
Persistence of the immune response
In a large clinical study performed two years after vaccination with two doses of Priorix Tetra, the seropositivity rate for varicella antibodies was 99.4% (ELISA) and 99.2% (IFA) and 99.2% respectively. , 1%, 90.5% and 100% for anti-measles, mumps and rubella antibodies (ELISA).
Post Marketing Security Surveillance Observational Study
The risk of febrile seizures following the first dose of Priorix Tetra was evaluated in a retrospective database analysis in children aged 9 to 30 months (see section 4.8).
05.2 Pharmacokinetic properties
Not applicable.
05.3 Preclinical safety data
A repeat dose toxicity study in animals revealed no local or systemic toxicity of the vaccine.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Dust:
Amino acids
Anhydrous lactose
Mannitol
Sorbitol
Medium 199
Solvent:
Water for injections
06.2 Incompatibility
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
06.3 Period of validity
18 months.
After reconstitution the vaccine should be injected immediately or stored in a refrigerator (2 ° C - 8 ° C). If it is not used within 24 hours it must be discarded.
06.4 Special precautions for storage
Store and transport refrigerated (2 ° C - 8 ° C).
Do not freeze.
Store in the original package to keep it away from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
06.5 Nature of the immediate packaging and contents of the package
Powder in vial (type I glass) with a stopper (butyl rubber).
0.5 ml of solvent in a pre-filled syringe (type I glass) with a plunger stopper (rubber butyl) with or without separate needles in the following pack sizes:
- without needles: packs of 1.10, 20 or 50.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
The reconstituted vaccine should be visually inspected for foreign particles and / or changes in physical appearance prior to administration.
If the above are observed, the vaccine should be discarded.
The vaccine must be reconstituted by adding the entire contents of the pre-filled solvent syringe supplied to the vial containing the powder. To insert the needle into the syringe, refer to the drawing below. However, the syringe supplied with Priorix Tetra may be slightly different (without thread) than the syringe described in the drawing.
In this case, the needle must be inserted without screwing.
1. While holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by turning it counterclockwise.
2. To connect the needle to the syringe, turn the needle in the syringe clockwise until it stops (see illustration).
3. Remove the needle guard, which on occasion can be a bit difficult.
Add the solvent to the powder. After adding the solvent to the powder, the mixture should be well stirred until the powder is completely dissolved in the solvent.
The color of the reconstituted vaccine can vary from light peach to fuchsia pink due to slight variations in its pH. This is normal and does not affect the efficacy of the vaccine. If other changes are observed, discard the vaccine.
A new needle must be used to administer the vaccine.
Inject the entire contents of the vial.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
GlaxoSmithKline S.p.A. - Via A. Fleming, 2 - 37135 Verona (Italy)
08.0 MARKETING AUTHORIZATION NUMBER
Packaging:
A.I.C .: 038200010 "powder and solvent for solution for injection" 1 vial powder + 1 pre-filled syringe of 0.5 ml solvent without needle
A.I.C .: 038200022 "powder and solvent for solution for injection" 10 vials powder + 10 pre-filled syringes of 0.5 ml solvent without needle
A.I.C .: 038200034 "powder and solvent for solution for injection" 20 vials powder + 20 pre-filled syringes of 0.5 ml solvent without needle
A.I.C .: 038200046 "powder and solvent for solution for injection" 50 vials powder + 50 pre-filled syringes of 0.5 ml solvent without needle
A.I.C .: 038200059 "powder and solvent for solution for injection" 1 vial powder + 1 pre-filled syringe of 0.5 ml solvent (with 2 needles)
A.I.C .: 038200061 "powder and solvent for solution for injection" 10 vials powder + 10 pre-filled syringes of 0.5 ml solvent (with 2 needles)
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
1 February 2008/21 June 2012
10.0 DATE OF REVISION OF THE TEXT
November 2016
