Priorix – Powder and solvent for solution for injection in a pre-filled syringe

Addition of statements regarding excipients of known pharmaceutical effect, as required by the European Guideline “Excipients in the labelling and package leaflet of medicinal product for human use” and its Annex.

 2           What you need to know before you receive Priorix

Added the following sub-heading and excipient statements:

Priorix contains sorbitol, para-aminobenzoic acid, phenylalanine, sodium and potassium

This vaccine contains 9 mg of sorbitol per dose.

Priorix contains para-aminobenzoic acid. It may cause allergic reactions (possibly delayed), and exceptionally, bronchospasm.

This vaccine contains 334 micrograms of phenylalanine per dose. Phenylalanine may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

The vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

The vaccine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially ‘potassium-free’.

6           Contents of the pack and other information

Under the sub-heading ‘The other ingredients are’:

Added the detail ‘containing phenylaniline’ to the excipient ‘Amino acids’

Added the E-numbers for Mannitol (E 421) and Sorbitol (E 420)

Added the following excipient detail, ‘Medium 199 (containing phenylalanine, para-aminobenzoic acid, sodium and potassium)’

Changed the revision date of the leaflet to 02/2022

Addition of statements regarding excipients of known pharmaceutical effect, as required by the European Guideline “Excipients in the labelling and package leaflet of medicinal product for human use” and its Annex.

2.          QUALITATIVE AND QUANTITATIVE COMPOSITION

Added the statement ‘The vaccine contains 6.5 nanograms of para-aminobenzoic acid per dose and 334 micrograms of phenylalanine per dose (see section 4.4).’

4.4        Special warnings and precautions for use

Added the following sub-heading and statements:

Excipients with known effects

Priorix contains para-aminobenzoic acid. It may cause allergic reactions (possibly delayed), and exceptionally, bronchospasm.

The vaccine contains 334 micrograms of phenylalanine per dose. Phenylalanine may be harmful for individuals with phenylketonuria (PKU).

The vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

The vaccine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially ‘potassium-free’.

Added the following sub-heading and advice:

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

6.1        List of excipients

Added the detail ‘containing phenylaniline’ to the excipient ‘Amino acids’

Added the E-numbers for Mannitol (E 421) and Sorbitol (E 420)

Added the following excipient detail, ‘Medium 199 (containing phenylalanine, para-aminobenzoic acid, sodium and potassium)’.

10.        DATE OF REVISION OF THE TEXT

Changed to 30 April 2022

Information directed to healthcare professionals: Added information on the use and handling of Plastic Rigid Tip Cap (PRTC) syringes containing the solvent used for the reconstitution of the vaccine.

Section 4: Updated the HPRA details for adverse event reporting.

Section 6: Changed the date of revision to 10/2019.

Section 6.6: Added information on the use and handling of Plastic Rigid Tip Cap (PRTC) syringes containing the solvent used for the reconstitution of the vaccine.

Section 4.8: Updated the HPRA details for adverse event reporting.

Section 10: Changed the date of revision to 19 December 2019.

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

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

, 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.

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’.

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”