Section 2: Minor formatting and editorial changes.

Section 4.2: Method of adminsitration updated to include in the deltoid region or in the anterolateral area of the thigh.
 
Section 4.4: Deleted information regarding patients with rare hereditary problems of fructose intolerance should not be vaccinated with PRIORIX since it contains sorbitol.

Section 4.5:
Updated the monovalent or combination vaccines that Priorix can be given with.
Information about why Priorix should be given at a separate injection site when given co-administered with Bexsero and other vaccines.
There are no data to support the use of PRIORIX with any other vaccines.

Section 4.8: Formatting changes. List of AE's is now in tabulated format.

Section 6.6: Minor formatting changes

Update section 4.3 and 4.8 of the SPC to better reflect data available in the literature and to harmonise or clarify the current product information.

Update to section 6.6 to bring an alignment on Priorix-Tetra and Varilrix in this section

Update to section 10 – revision date updated

Section 7 - change to address of the Irish MA Holder from Stonemasons Way, Rathfarnham, Dublin 16 to 12 Riverwalk, Citywest Business Campus, Dublin 24.

Section 10 - change to date of revision of text.

 

Changes to:

Section 4.8 - Undesirable effects,
Section 6.6 - Special precautions for disposal,
Section 6.1 - List of excipients

4.3          Contraindications

 

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or neomycin. A history of contact dermatitis to neomycin is not a contraindication. For hypersensitivity reactions to egg proteins, see section 4.4.

 

Severe Hhumoral or cellular immune deficiency (primary or acquired) immunodeficiency, including hypogammaglobulinaemia, dysgammaglobulinaemia e.g. severe combined immunodeficiency, agammaglobulinemia and AIDS or symptomatic HIV infection or an age-specific CD4+ T-lymphocyte percentage in children below 12 months: CD4+ <25%; children between 12-35 months: CD4+ < 20%; children between 36-59 months: CD4+ < 15% (see section 4.4).

 

Pregnancy. Furthermore, pregnancy should be avoided for 1 month following vaccination (see section 4.6).

 

As with other vaccines, the administration of PRIORIX should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection, such as a cold, should not result in the deferral of vaccination.

 

 

4.4          Special warnings and precautions for use

 

Immunocompromised patients

Vaccination may be considered in patients with selected immune deficiencies where the benefits outweigh the risks (e.g. asymptomatic HIV subjects, IgG subclass deficiencies, congenital neutropenia, chronic granulomatous disease and complement deficiency diseases).

 

Immunocompromised patients who have no contraindication for this vaccination (see section 4.3) may not respond as well as immunocompetent subjectspatients, therefore some of these patients may acquire measles, mumps or rubella in case of contact, despite appropriate vaccine administration. These patients should be monitored carefully for signs of measles, parotitis and rubella.

 

 

4.6          Fertility, pregnancy and lactation

 

Pregnancy

Pregnant women should not be vaccinated with PRIORIX.

 

However, fetal damage has not been documented when measles, mumps or rubella vaccines have been given to pregnant women.

Even if a theoretical risk cannot be excluded yet, no cases of congenital rubella syndrome have been reported in more than 3500 susceptible women who were unknowingly in early stages of pregnancy when vaccinated with rubella containing vaccines. Therefore, inadvertent vaccination of unknowingly pregnant women with measles, mumps and rubella containing vaccines should not be a reason for termination of pregnancy.

Pregnancy should be avoided for 1 month following vaccination. Women who intend to become pregnant should be advised to delay.

 

PRIORIX is contraindicated during pregnancy (see section 4.3). However foetal damage has not been documented when measles, mumps and rubella vaccines have been given to women who were unknowingly in early stages of pregnancy.

 

Women of Childbearing Potential

 

Women who intend to become pregnant should be advised to delay for 1 month following PRIORIX vaccination. Although women should be asked about the possibility of early pregnancy prior to vaccination, screening tests to exclude pregnancy are not required. Inadvertent vaccination of unknowingly pregnant women with PRIORIX should not be a reason for termination of pregnancy.

 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Added the following statement re neomycin:

This vaccine contains a trace amount of neomycin. See section 4.3.

5.1 Pharmacodynamic properties

Added the seroconversion rate for rubella, i.e.:

The seroconversion rates reported following the second dose given 3 months after the first dose were 100% for measles

 

, and 99.2% for mumps and 100% for rubella. Therefore a second dose of PRIORIX should be given within three months to provide optimal immune responses.

 

6.1 List of excipients

Updated the list of excipients, (deleting Phenol red, Sodium chloride, Potassium chloride, Magnesium sulphate, Calcium chloride, Potassium di-hydrogen phosphate, Di-sodium hydrogen phosphate), to read:

Vaccine:

Amino acids

Lactose (anhydrous)

Mannitol

Sorbitol

Solvent:

Water for injections

4.4       Special warnings and precautions for use

Added the following warning

Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

2.             Qualitative And Quantitative Composition

Added the following:

Excipients with known effect:

The vaccine contains 9 mg of sorbitol, see section 4.4.

 

4.1       Therapeutic indications

Changed the lower age limit from 11 months to 9 months

 

Revised statement and references regarding use in children from 9-10 months of age to the following, widening the age limits to 9 to 12 months to read as follows:

For use in children between 9 to 12 months of age see sections 4.2, 4.4 and 5.1.

 

4.2       Posology and method of administration

Included the statement that:

The use of PRIORIX should be based on official recommendations.

 

Updated Posology details under the following age specific sub-headings and with corresponding instructions:

Individuals 12 months of age or older

Infants between 9 and 12 months of age

Infants less than 9 months of age

 

Added the administration instruction regarding subcutaneous administration:

The vaccine should preferably be administered subcutaneously in patients with thrombocytopenia or any coagulation disorder (see section 4.4).

 

4.3       Contraindications

Updated the contraindication statements regarding use in subjects with impaired immune systems or HIV infection to read:

Humoral or cellular immune deficiency (primary or acquired), including hypogammaglobulinaemia, dysgammaglobulinaemia and AIDS or symptomatic HIV infection or an age-specific CD4+ T-lymphocyte percentage in children below 12 months: CD4+ <25%; children between 12-35 months: CD4+ < 20%; children between 36-59 months: CD4+ < 15% (see section 4.4).

 

Updated the statement to clearly contraindicate all use in pregnancy, and added a reference to section 4.6 of the SPC.

 

4.4       Special warnings and precautions for use

Deleted the following statement regarding vaccination of infants in their first year in an epidemiological situation:

In case an epidemiological situation requires vaccinating infants in their first year of life, a second dose of PRIORIX is recommended, preferably three months after the first dose. Under no circumstances should the interval between doses be less than four weeks.

 

Updated the statement and advice on use in individuals with CNS disorder, susceptibility to febrile convulsions or family history of convulsion, to read:

Due caution should be employed in administration of PRIORIX to individuals with Central Nervous System (CNS) disorder, susceptibility to febrile convulsions or family history of convulsions. Vaccinees with a history of febrile convulsions should be closely followed-up.

 

The following warning was added regarding patients with fructose intolerance:

Patients with rare hereditary problems of fructose intolerance should not be vaccinated with PRIORIX since it contains sorbitol.

 

Removed the following warning regarding co-administration with other live attenuated vaccines:

If not given at the same time, an interval of at least one month is recommended between administration of PRIORIX and other live attenuated vaccines.

 

Added the following statement regarding vaccination post exposure to natural measles:

Limited protection against measles may be obtained by vaccination up to 72 hours after exposure to natural measles.

 

Added the following statement regarding protective immune response

As with any vaccine, a protective immune response may not be elicited in all vaccinees.

 

Added subheadings for Thrombocytopenia, Immunocompromised patients and Transmission

 

Under the subheading ‘Thrombocytopenia’ clarified that such patients should be vaccinated with caution and preferably using subcutaneous route.

 

Added the following warning regarding Immunocompromised patients

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 acquire measles, mumps or rubella in case of contact, despite appropriate vaccine administration. These patients should be monitored carefully for signs of measles, parotitis and rubella.

 

Added the following statement regarding the transmission of rubella:

Transmission of the rubella vaccine virus to infants via breast milk as well as transplacental transmission has been documented without any evidence of clinical disease.

 

4.5       Interaction with other medicinal products and other forms of interaction

Added the following  regarding vaccines with which Priorix can be co-administered:

PRIORIX can be given simultaneously (but at separate injection sites) with any of the following monovalent or combination vaccines [including hexavalent vaccines (DTPa-HBV-IPV/Hib)]: diphtheria-tetanus-acellular pertussis vaccine (DTPa), Haemophilus influenzae type b vaccine (Hib), inactivated polio vaccine (IPV), hepatitis B vaccine (HBV), hepatitis A vaccine (HAV), Meningococcal serotype C conjugated vaccine (MenC), varicella zoster  vaccine (VZV), oral polio vaccine (OPV) and 10-valent pneumococcal conjugate vaccine in accordance with local recommendations.

 

There are no data to support the use of PRIORIX with any other vaccines.

 

The above statements replaced the previous advice:

Combined measles, mumps and rubella vaccines can be given simultaneously with other vaccines in accordance with recommendations of vaccine advisory board of individual member states and/or medical practices. Separate injection sites should be used.

 

Updated the advice regarding admistration of Priorix in patients who have received human globulins to specify that vaccination should be delayed for up to 11 months dependiong on the dose of human globulins administered because of the likelihood of vaccine failure due to passively acquired measles, mumps and rubella antibodies.

 

 

4.6       Fertility, pregnancy and lactation

Included the statement that

PRIORIX has not been evaluated in fertility studies.

 

While PRIORIX is contraindicated during pregnancy the following statement was added regarding observations following administration of MMR vaccine to women in early stages of pregnancy:

However foetal damage has not been documented when measles, mumps and rubella vaccines have been given to women who were unknowingly in early stages of pregnancy.

 

Added the following statement regarding Women of Childbearing Potential

Women who intend to become pregnant should be advised to delay for 1 month following PRIORIX vaccination. Although women should be asked about the possibility of early pregnancy prior to vaccination, screening tests to exclude pregnancy are not required. Inadvertent vaccination of unknowingly pregnant women with PRIORIX should not be a reason for termination of pregnancy.

 

Added the following statement regarding breastfeeding:

There is limited experience with PRIORIX during breast-feeding. Studies have shown that breast-feeding postpartum women vaccinated with live attenuated rubella vaccines may secrete the virus in breast milk and transmit it to breast-fed infants without evidence of any symptomatic disease. Only in the event the child is confirmed or suspected to be immunodeficient, risks and benefits of vaccinating the mother should be evaluated (see section 4.3).

 

4.8       Undesirable effects

Rearranged the order of undesirable effects observed in Clinical Trials, no changes to the undesirable effecst of their frequencies.

 

Rearranged the order of undesirable effects observed in Post-marketing data placing ‘Kawasaki syndrome’ under the new heading ‘General disorders and administration site conditions’.

 

Added ‘orchitis, epididymitis, atypical mild or attenuated measles, mumps-like syndrome’ under the heading ‘Infections and infestations’:

 

Placing ‘atypical mild or attenuated measles, mumps-like syndrome’ under the heading ‘Infections and infestations’ replaced the previous statements regarding rare cases of mumps like condition and measles like syndrome.

 

5.1       Pharmacodynamic properties

Updated the data regarding ‘Immune response in children 12 months and older’ following vaccination with a single dose of PRIORIX induced antibodies in previously seronegative vaccinees:

• against measles from 98.0% to 98. 1%,
• against mumps from 96.1% to 94.4%,
• against rubella from 99.3% to 100% of.

 

Added the following statement regarding seroconversion rates and protective efficacy:

Two years after primary vaccination seroconversion rates were 93.4% for measles, 94.4% for mumps and 100% for rubella.

 

Although there are no data available concerning the protective efficacy of PRIORIX, immunogenicity is accepted as an indication of protective efficacy. However, some field studies report that the effectiveness against mumps may be lower than the observed seroconversion rates to mumps.

 

Updated the data regarding ‘Immune response in children aged 9 to 10 months’ with the advice that:

‘a second dose of PRIORIX should be given within three months to provide optimal immune responses’

 

Added the following statement regarding the route of administration:

A limited number of subjects received PRIORIX intramuscularly in clinical trials. The seroconversion rates to the three components were comparable to those seen after subcutaneous administration.

 

 

4.1       Therapeutic indications

Added reference to section 5.1 of the SPC.

 

4.4       Special warnings and precautions for use

Deleted paragraph regarding neomycin, i.e.:

Priorix contains small amounts of neomycin. The vaccine should be used with caution in subjects with known hypersensitivity to this excipient (see section 4.3).

 

Added the following paragraph regarding idiopathic thrombocytopenic purpura:

Cases of worsening of thrombocytopenia and cases of recurrence of thrombocytopenia in subjects who suffered thrombocytopenia after the first dose have been reported following vaccination with live measles, mumps and rubella vaccines. In such cases, the risk-benefit of immunising with Priorix should be carefully evaluated.

 

5.1       Pharmacodynamic properties

Added the following paragraph:

The immune response for measles and mumps were suboptimal in children 9 to 10 months of age. Seroconversion rates for measles and mumps were 94.4% and 92.0%, respectively. Therefore a second dose of PRIORIX should be given with a preferred interval of three months between the doses to have optimal immune responses. The seroconversion rate reported following the second dose was 100% for measles and 99.2% for mumps.

 

6.3       Shelf-life

Updated expression of shelf life from ‘24 months’ to ‘2 years’.

 

 

4.8 Safety profile updated based on an increased number of subjects in clinical trials (from 10000 to 12000.

- Side effects added:

Conjunctivitis (uncommon), allergic reactions (rare, previously detailed in Post-Marketing Surveillance section)

- Side effects deleted

Somnolence, rhinitis, other viral infections, malaise

- Side effect frequency changes

Uncommon to common: Upper respiratory tract infection

Common to uncommon: Nervousness

Uncommon to rare: Febrile reactions

Comment included regarding the frequency of 'pain at the injection site' as common for the first dose and very common for the second dose.

- Post-marketing surveillance:

Allergic reactions deleted and moved to Clinical Trials section as rare side effect.

Comment included regarding the frequency and risk of encephalitis from the vaccine is as far lower than the risk caused by natural diseases.

- Added: Measles like syndrome

4.9 Overdose statement updated from no cases to cases where up to 2 times the recommended dose had been administered and no cases of adverse events were reported with overdose.

Section 6.3

Shelf-Life has cahnged from 18 months to 24 months.

Updates re side effects (SPC section 4.8 and PL) and overdose (SPC section 4.9 only):

4.8 Safety profile updated based on an increased number of subjects in clinical trials (from 10000 to 12000.

- Side effects added:

Conjunctivitis (uncommon), allergic reactions (rare, previously detailed in Post-Marketing Surveillance section)

- Side effects deleted

Somnolence, rhinitis, other viral infections, malaise

- Side effect frequency changes

Uncommon to common: Upper respiratory tract infection

Common to uncommon: Nervousness

Uncommon to rare: Febrile reactions

Comment included regarding the frequency of 'pain at the injection site' as common for the first dose and very common for the second dose.

- Post-marketing surveillance:

Allergic reactions deleted and moved to Clinical Trials section as rare side effect.

Comment included regarding the frequency and risk of encephalitis from the vaccine is as far lower than the risk caused by natural diseases.

- Added: Measles like syndrome

4.9 Overdose statement updated from no cases to cases where up to 2 times the recommended dose had been administered and no cases of adverse events were reported with overdose.

Shelf life extended from 18 months to 24 months.

Labelling and User Testing:

Sections 1 and 3 of SPC: slight change in approved name to include 'pre-filled syringe'.

Section 4.8 of SPC: Rearrangement of side effects; no change to side effects, categories or frequencies.

Section 6.5 of SPC: Greater description of pack sizes incude

To update SPC section 4.5 of the SPC on concomitant administration of Rotarix with oral poliovirus (OPV) vaccine based on data from a clinical study evaluating the concomitant use of Rotarix with routine WHO expanded program of immunisation (EPI) vaccinations in healthy infants.

To update SPC section 5.1: Inclusion of Pharmacodynamic data as a result of Study 32; adds data from the 2nd year of life.

Correction to Section 4.4 of SPC: Inclusion of clarification in the warning regarding apnoea in very premature children that 'administering immunisation' should read 'administering the primary immunisation'.

Section 1 moved 'powder and solvent  for solution for injection' from immediately after 'priorix' to next line.

 

 Section 2 moved (RIT 4385 strain, derived from Jeryl Lynn strain) to the next line.

 

Section 9

 

Added “Date of last renewal: 25^th November 2007”

 

Section 10

 

Added “June 2008”