4.1. Therapeutic indications

PRIORIX is indicated for active immunisation of children from the age of 9 months or older, adolescents and adults against measles, mumps and rubella.

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

Posology

The use of PRIORIX should be based on official recommendations.

Individuals 12 months of age or older

The dose is 0.5 ml. A second dose should be given according to official recommendations.

PRIORIX may be used in individuals who have previously been vaccinated with another monovalent or combined measles, mumps and rubella vaccine.

Infants between 9 and 12 months of age

Infants in their first year of life may not respond sufficiently to the components of the vaccines. In case an epidemiological situation requires vaccinating infants in their first year of life (e.g. outbreak or travel to endemic regions), a second dose of PRIORIX should be given in the second year of life, preferably within three months after the first dose. Under no circumstances should the interval between doses be less than four weeks (see sections 4.4 and 5.1).

Infants less than 9 months of age

The safety and efficacy of PRIORIX in infants under 9 months of age has not been established.

Method of administration

PRIORIX is for subcutaneous injection, although it can also be given by intramuscular injection, in the deltoid region or in the anterolateral area of the thigh (see sections 4.4 and 5.1).

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

For instructions on reconstitution of the medicinal product before administration see section 6.6.

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.

Current immunosuppressive therapy (including high doses of corticosteroids). Priorix is not contraindicated in individuals who are receiving topical or low-dose parenteral corticosteroids (e.g. for asthma prophylaxis or replacement therapy).

Severe humoral or cellular (primary or acquired) immunodeficiency, 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+ < 2 0%; 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

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.

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 in their first year of life may not respond sufficiently to the components of the vaccine, due to the possible interference with maternal antibodies (see sections 4.2 and 5.1).

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 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 reactions (e.g. generalised urticaria, swelling of the mouth and throat, difficulty in 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 egg ingestion should be vaccinated with extreme caution, with adequate treatment for anaphylaxis on hand should such a reaction occur.

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

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.

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

PRIORIX SHOULD UNDER NO CIRCUMSTANCES BE ADMINISTERED INTRAVASCULARLY.

Thrombocytopenia

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. MMR-associated thrombocytopenia is rare and generally self-limited. In patients with existing thrombocytopenia or a history of thrombocytopenia after measles, mumps or rubella vaccination the risk-benefit of administering PRIORIX should be carefully evaluated. These patients should be vaccinated with caution and preferably using subcutaneous route.

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 subjects, 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.

Transmission

Transmission of measles and mumps virus from vaccinees to susceptible contacts has never been documented. Pharyngeal excretion of the rubella and measles virus is known to occur about 7 to 28 days after vaccination with peak excretion around the 11th day. However there is no evidence of transmission of these excreted vaccine viruses to susceptible contacts. 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.

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'.

4.5. Interaction with other medicinal products and other forms of interaction

Clinical studies have demonstrated that PRIORIX can be given simultaneously with any of the following monovalent or combination vaccines [including hexavalent vaccines (DTPa-HBV-IPV/Hib)]: diphtheria-tetanus-acellular pertussis vaccine (DTPa), reduced antigen 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 serogroup B vaccine (MenB), meningococcal serogroup C conjugate vaccine (MenC), meningococcal serogroups A, C, W-135 and Y conjugate vaccine (MenACWY), varicella zoster vaccine (VZV), oral polio vaccine (OPV) and pneumococcal conjugate vaccine in accordance with local recommendations.

Due to an increased risk of fever, tenderness at the injection site, change in eating habits and irritability when Bexsero was co-administered with a combined measles-mumps-rubella-varicella (MMR-V) vaccine, separate vaccination with PRIORIX can be considered when possible.

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

If PRIORIX is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

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.

If tuberculin testing has to be done it should be carried out before or simultaneously with vaccination since it has been reported that combined measles, mumps and rubella vaccines may cause a temporary depression of tuberculin skin sensitivity. As this anergy may last up to a maximum of 6 weeks, tuberculin testing should not be performed within that period after vaccination to avoid false negative results.

In subjects who have received human gammaglobulins or a blood transfusion, vaccination should be delayed for three months or longer (up to 11 months) depending 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

Fertility

PRIORIX has not been evaluated in fertility studies.

Pregnancy

Pregnant women should not be vaccinated with PRIORIX.

Studies have not been conducted with Priorix in pregnant women.

In a review of more than 3 500 susceptible women who were unknowingly in early stages of pregnancy when vaccinated with a rubella-containing vaccine, no cases of congenital rubella syndrome were reported. Subsequent post-marketing surveillance identified congenital rubella syndrome associated with a rubella vaccine strain (Wistar RA 27/3) following inadvertent vaccination of a pregnant woman with a measles, mumps and rubella vaccine.

Foetal damage has not been documented when measles or mumps vaccines have been given to pregnant women.

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

Breast-feeding

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).

4.7. Effects on ability to drive and use machines

PRIORIX has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

Summary of the safety profile

The safety profile presented below is based on a total of approximately 12 000 subjects administered PRIORIX in clinical trials.

Adverse reactions which might occur following the use of a combined mumps, measles, rubella vaccine correspond to those observed after administration of the monovalent vaccines alone or in combination.

In controlled clinical studies, signs and symptoms were actively monitored during a 42-day follow-up period. The vaccinees were also requested to report any clinical events during the study period.

The most common adverse reactions following PRIORIX administration were injection site redness and fever ≥38 °C (rectal) or ≥37.5 °C (axillary/oral).

Tabulated list of adverse reactions

Adverse reactions reported are listed according to the following frequency:

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)

Clinical trial data

System Organ Class

Frequency

Adverse reactions

Infections and infestations

Common

upper respiratory tract infection

Uncommon

otitis media

Blood and lymphatic system disorders

Uncommon

lymphadenopathy

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

parotid gland enlargement, diarrhoea, vomiting

Skin and subcutaneous tissue disorders

Common

rash

General disorders and administration site conditions

Very common

redness 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 category for adverse reactions was similar for the first and second vaccine doses. The exception to this was pain at the injection site which was “Common” after the first vaccine dose and “Very common” after the second vaccine dose.

Post-marketing data

The following adverse reactions have been identified in rare occasions during post-marketing surveillance. Because they are reported voluntarily from a population of unknown size, a true estimate of frequency cannot be provided.

System Organ Class

Adverse reactions

Infections and infestations

Meningitis, measles-like syndrome, mumps-like syndrome (including orchitis, epididymitis and parotitis)

Blood and lymphatic system disorders

Thrombocytopenia, thrombocytopenic purpura

Immune system disorders

Anaphylactic reactions

Nervous system disorders

Encephalitis*, cerebellitis, cerebellitis like symptoms (including transient gait disturbance and transient ataxia), Guillain-Barré syndrome, transverse myelitis, peripheral neuritis

Vascular disorders

Vasculitis

Skin and subcutaneous tissue disorders

Erythema multiforme

Musculoskeletal and connective tissue disorders

Arthralgia, arthritis

* Encephalitis has been reported with a frequency below 1 per 10 million doses. The risk of encephalitis following administration of the vaccine is far below the risk of encephalitis caused by natural diseases (measles: 1 in 1 000 to 2 000 cases; mumps: 2-4 in 1 000 cases; rubella: approximately 1 in 6 000 cases).

Accidental intravascular administration may give rise to severe reactions or even shock. Immediate measures depend on the severity of the reaction (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Cases of overdose (up to 2 times the recommended dose) have been reported during post-marketing surveillance. No adverse events have been associated to the overdose.